start-ver=1.4
cd-journal=joma
no-vol=10
cd-vols=
no-issue=
article-no=
start-page=1261330
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=20230907
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=In vivo tracking transplanted cardiomyocytes derived from human induced pluripotent stem cells using nuclear medicine imaging
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Introduction: Transplantation of human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) is a promising treatment for heart failure. Information on long-term cell engraftment after transplantation is clinically important. However, clinically applicable evaluation methods have not yet been established.<br>
Methods: In this study, to noninvasively assess transplanted cell engraftment, human SLC5A5, which encodes a sodium/iodide symporter (NIS) that transports radioactive tracers such as 125I, 18F-tetrafluoroborate (TFB), and 99mTc-pertechnetate (99mTcO4−), was transduced into human induced pluripotent stem cells (iPSCs), and nuclear medicine imaging was used to track engrafted human iPSC-CMs.<br>
Results: To evaluate the pluripotency of NIS-expressing human iPSCs, they were subcutaneously transplanted into immunodeficient rats. Teratomas were detected by 99mTcO4− single photon emission computed tomography (SPECT/CT) imaging. NIS expression and the uptake ability of 125I were maintained in purified human iPSC-CMs. NIS-expressing human iPSC-CMs transplanted into immunodeficient rats could be detected over time using 99mTcO4− SPECT/CT imaging. Unexpectedly, NIS expression affected cell proliferation of human iPSCs and iPSC-derived cells.<br>
Discussion: Such functionally designed iPSC-CMs have potential clinical applications as a noninvasive method of grafted cell evaluation, but further studies are needed to determine the effects of NIS transduction on cellular characteristics and functions.
en-copyright=
kn-copyright=

en-aut-name=SaitoYukihiro
en-aut-sei=Saito
en-aut-mei=Yukihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=NoseNaoko
en-aut-sei=Nose
en-aut-mei=Naoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=IidaToshihiro
en-aut-sei=Iida
en-aut-mei=Toshihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=AkazawaKaoru
en-aut-sei=Akazawa
en-aut-mei=Kaoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=KannoTakayuki
en-aut-sei=Kanno
en-aut-mei=Takayuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=FujimotoYuki
en-aut-sei=Fujimoto
en-aut-mei=Yuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=SasakiTakanori
en-aut-sei=Sasaki
en-aut-mei=Takanori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=AkehiMasaru
en-aut-sei=Akehi
en-aut-mei=Masaru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=HiguchiTakahiro
en-aut-sei=Higuchi
en-aut-mei=Takahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=AkagiSatoshi
en-aut-sei=Akagi
en-aut-mei=Satoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=YoshidaMasashi
en-aut-sei=Yoshida
en-aut-mei=Masashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=MiyoshiToru
en-aut-sei=Miyoshi
en-aut-mei=Toru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=ItoHiroshi
en-aut-sei=Ito
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=NakamuraKazufumi
en-aut-sei=Nakamura
en-aut-mei=Kazufumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

affil-num=1
en-affil=Department of Cardiovascular Medicine, Okayama University Hospital
kn-affil=

affil-num=2
en-affil=Molecular Imaging Project of RECTOR Program, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=3
en-affil=Department of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=4
en-affil=Department of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=5
en-affil=Molecular Imaging Project of RECTOR Program, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=6
en-affil=Molecular Imaging Project of RECTOR Program, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=7
en-affil=Okayama Medical Innovation Center, Faculty of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=8
en-affil=Okayama Medical Innovation Center, Faculty of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=9
en-affil=Molecular Imaging Project of RECTOR Program, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=10
en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=11
en-affil=Department of Chronic Kidney Disease and Cardiovascular Disease, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=12
en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=13
en-affil=Department of General Internal Medicine 3, Kawasaki Medical School
kn-affil=

affil-num=14
en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=sodium/iodide symporter
kn-keyword=sodium/iodide symporter
en-keyword=human induced pluripotent stem cell-derived cardiomyocytes
kn-keyword=human induced pluripotent stem cell-derived cardiomyocytes
en-keyword=single photon emission computed tomography
kn-keyword=single photon emission computed tomography
en-keyword=cell-based therapy
kn-keyword=cell-based therapy
en-keyword=in vivo imaging
kn-keyword=in vivo imaging
END

start-ver=1.4
cd-journal=joma
no-vol=15
cd-vols=
no-issue=2
article-no=
start-page=690
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=20230217
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Rationalizing the Binding Modes of PET Radiotracers Targeting the Norepinephrine Transporter
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Purpose: A new PET radiotracer F-18-AF78 showing great potential for clinical application has been reported recently. It belongs to a new generation of phenethylguanidine-based norepinephrine transporter (NET)-targeting radiotracers. Although many efforts have been made to develop NET inhibitors as antidepressants, systemic investigations of the structure-activity relationships (SARs) of NET-targeting radiotracers have rarely been performed. Methods: Without changing the phenethylguanidine pharmacophore and 3-fluoropropyl moiety that is crucial for easy labeling, six new analogs of F-18-AF78 with different meta-substituents on the benzene-ring were synthesized and evaluated in a competitive cellular uptake assay and in in vivo animal experiments in rats. Computational modeling of these tracers was established to quantitatively rationalize the interaction between the radiotracers and NET. Results: Using non-radiolabeled reference compounds, a competitive cellular uptake assay showed a decrease in NET-transporting affinity from meta-fluorine to iodine (0.42 and 6.51 mu M, respectively), with meta-OH being the least active (22.67 mu M). Furthermore, in vivo animal studies with radioisotopes showed that heart-to-blood ratios agreed with the cellular experiments, with AF78(F) exhibiting the highest cardiac uptake. This result correlates positively with the electronegativity rather than the atomic radius of the meta-substituent. Computational modeling studies revealed a crucial influence of halogen substituents on the radiotracer-NET interaction, whereby a T-shaped pi-pi stacking interaction between the benzene-ring of the tracer and the amino acid residues surrounding the NET binding site made major contributions to the different affinities, in accordance with the pharmacological data. Conclusion: The SARs were characterized by in vitro and in vivo evaluation, and computational modeling quantitatively rationalized the interaction between radiotracers and the NET binding site. These findings pave the way for further evaluation in different species and underline the potential of AF78(F) for clinical application, e.g., cardiac innervation imaging or molecular imaging of neuroendocrine tumors.
en-copyright=
kn-copyright=

en-aut-name=TutovAnna
en-aut-sei=Tutov
en-aut-mei=Anna
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=ChenXinyu
en-aut-sei=Chen
en-aut-mei=Xinyu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=WernerRudolf A.
en-aut-sei=Werner
en-aut-mei=Rudolf A.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=MuehligSaskia
en-aut-sei=Muehlig
en-aut-mei=Saskia
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=ZimmermannThomas
en-aut-sei=Zimmermann
en-aut-mei=Thomas
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=NoseNaoko
en-aut-sei=Nose
en-aut-mei=Naoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=KoshinoKazuhiro
en-aut-sei=Koshino
en-aut-mei=Kazuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=LapaConstantin
en-aut-sei=Lapa
en-aut-mei=Constantin
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=DeckerMichael
en-aut-sei=Decker
en-aut-mei=Michael
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=HiguchiTakahiro
en-aut-sei=Higuchi
en-aut-mei=Takahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

affil-num=1
en-affil=Pharmaceutical and Medicinal Chemistry, Institute of Pharmacy and Food Chemistry, University of Würzburg
kn-affil=

affil-num=2
en-affil=Nuclear Medicine, Faculty of Medicine, University of Augsburg
kn-affil=

affil-num=3
en-affil=Department of Nuclear Medicine and Comprehensive Heart Failure Center, University Hospital Würzburg
kn-affil=

affil-num=4
en-affil=Department of Nuclear Medicine and Comprehensive Heart Failure Center, University Hospital Würzburg
kn-affil=

affil-num=5
en-affil=Pharmaceutical and Medicinal Chemistry, Institute of Pharmacy and Food Chemistry, University of Würzburg
kn-affil=

affil-num=6
en-affil=Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=7
en-affil=Department of Systems and Informatics, Hokkaido Information University
kn-affil=

affil-num=8
en-affil=Nuclear Medicine, Faculty of Medicine, University of Augsburg
kn-affil=

affil-num=9
en-affil=Pharmaceutical and Medicinal Chemistry, Institute of Pharmacy and Food Chemistry, University of Würzburg
kn-affil=

affil-num=10
en-affil=Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=positron emission tomography
kn-keyword=positron emission tomography
en-keyword=norepinephrine transporter
kn-keyword=norepinephrine transporter
en-keyword=sympathetic nervous system
kn-keyword=sympathetic nervous system
en-keyword=structure-activity relationships
kn-keyword=structure-activity relationships
en-keyword=T-shaped π–π stacking
kn-keyword=T-shaped π–π stacking
END

start-ver=1.4
cd-journal=joma
no-vol=2022
cd-vols=
no-issue=
article-no=
start-page=9810097
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220716
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Performance Evaluation of a Preclinical SPECT Scanner with a Collimator Designed for Medium-Sized Animals
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background. Equipped with two stationary detectors, a large bore collimator for medium-sized animals has been recently introduced for dedicated preclinical single-photon emission computed tomography (SPECT) imaging. We aimed to evaluate the basic performance of the system using phantoms and healthy rabbits. Methods. A general-purpose medium-sized animal (GP-MSA) collimator with 135 mm bore diameter and thirty-three holes of 2.5 mm diameter was installed on an ultrahigh-resolution scanner equipped with two large stationary detectors (U-SPECT5-E/CT). The sensitivity and uniformity were investigated using a point source and a cylinder phantom containing Tc-99m-pertechnetate, respectively. Uniformity (in %) was derived using volumes of interest (VOIs) on images of the cylinder phantom and calculated as maximum count-minimum count/maximum count+minimum countx100, with lower values of % indicating superior performance. The spatial resolution and contrast-to-noise ratios (CNRs) were evaluated with images of a hot-rod Derenzo phantom using different activity concentrations. Feasibility of in vivo SPECT imaging was finally confirmed by rabbit imaging with the most commonly used clinical myocardial perfusion SPECT agent [Tc-99m]Tc-sestamibi (dynamic acquisition with a scan time of 5 min). Results. In the performance evaluation, a sensitivity of 790 cps/MBq, a spatial resolution with the hot-rod phantom of 2.5 mm, and a uniformity of 39.2% were achieved. The CNRs of the rod size 2.5 mm were 1.37, 1.24, 1.20, and 0.85 for activity concentration of 29.2, 1.0, 0.5, and 0.1 MBq/mL, respectively. Dynamic SPECT imaging in rabbits allowed to visualize most of the thorax and to generate time-activity curves of the left myocardial wall and ventricular cavity. Conclusion. Preclinical U-SPECT5-E/CT equipped with a large bore collimator demonstrated adequate sensitivity and resolution for in vivo rabbit imaging. Along with its unique features of SPECT molecular functional imaging is a superior collimator technology that is applicable to medium-sized animal models and thus may promote translational research for diagnostic purposes and development of novel therapeutics.
en-copyright=
kn-copyright=

en-aut-name=MatsusakaYohji
en-aut-sei=Matsusaka
en-aut-mei=Yohji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=WernerRudolf A.
en-aut-sei=Werner
en-aut-mei=Rudolf A.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=Arias-LozaPaula
en-aut-sei=Arias-Loza
en-aut-mei=Paula
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=NoseNaoko
en-aut-sei=Nose
en-aut-mei=Naoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=SasakiTakanori
en-aut-sei=Sasaki
en-aut-mei=Takanori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=ChenXinyu
en-aut-sei=Chen
en-aut-mei=Xinyu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=LapaConstantin
en-aut-sei=Lapa
en-aut-mei=Constantin
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=HiguchiTakahiro
en-aut-sei=Higuchi
en-aut-mei=Takahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

affil-num=1
en-affil= Department of Nuclear Medicine and Comprehensive Heart Failure Center, University Hospital of Würzburg
kn-affil=

affil-num=2
en-affil= Department of Nuclear Medicine and Comprehensive Heart Failure Center, University Hospital of Würzburg
kn-affil=

affil-num=3
en-affil= Department of Nuclear Medicine and Comprehensive Heart Failure Center, University Hospital of Würzburg
kn-affil=

affil-num=4
en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=5
en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=6
en-affil=Department of Nuclear Medicine and Comprehensive Heart Failure Center, University Hospital of Würzburg
kn-affil=

affil-num=7
en-affil=Nuclear Medicine, Medical Faculty, University of Augsburg
kn-affil=

affil-num=8
en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
END

start-ver=1.4
cd-journal=joma
no-vol=2022
cd-vols=
no-issue=
article-no=
start-page=4635171
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220621
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=In Vivo Functional Assessment of Sodium-Glucose Cotransporters (SGLTs) Using [F-18]Me4FDG PET in Rats
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background. Mediating glucose absorption in the small intestine and renal clearance, sodium glucose cotransporters (SGLTs) have emerged as an attractive therapeutic target in diabetic patients. A substantial fraction of patients, however, only achieve inadequate glycemic control. Thus, we aimed to assess the potential of the SGLT-targeting PET radiotracer alpha-methyl-4-deoxy-4-[F-18]fluoro-D-glucopyranoside ([F-18]Me4FDG) as a noninvasive intestinal and renal biomarker of SGLT-mediated glucose transport. Methods. We investigated healthy rats using a dedicated small animal PET system. Dynamic imaging was conducted after administration of the reference radiotracer 2-deoxy-2-[F-18]fluoro-D-glucose ([F-18]FDG), or the SGLT-targeting agent, [F-18]Me4FDG either directly into the digestive tract (for assessing intestinal absorption) or via the tail vein (for evaluating kidney excretion). To confirm the specificity of [F-18]Me4FDG and responsiveness to treatment, a subset of animals was also pretreated with the SGLT inhibitor phlorizin. In this regard, an intraintestinal route of administration was used to assess tracer absorption in the digestive tract, while for renal assessment, phlorizin was injected intravenously (IV). Results. Serving as reference, intestinal administration of [F-18]FDG led to slow absorption with retention of 89.2 +/- 3.5% of administered radioactivity at 15 min. [F-18]Me4FDG, however, was rapidly absorbed into the blood and cleared from the intestine within 15 min, leading to markedly lower tracer retention of 18.5 +/- 1.2% (P < 0.0001). Intraintestinal phlorizin led to marked increase of [F-18]Me4FDG uptake (15 min, 99.9 +/- 4.7%; P < 0.0001 vs. untreated controls), supporting the notion that this PET agent can measure adequate SGLT inhibition in the digestive tract. In the kidneys, radiotracer was also sensitive to SGLT inhibition. After IV injection, [F-18]Me4FDG reabsorption in the renal cortex was significantly suppressed by phlorizin when compared to untreated animals (%ID/g at 60 min, 0.42 +/- 0.10 vs. untreated controls, 1.20 +/- 0.03; P < 0.0001). Conclusion. As a noninvasive read-out of the concurrent SGLT expression in both the digestive tract and the renal cortex, [F-18]Me4FDG PET may serve as a surrogate marker for treatment response to SGLT inhibition. As such, [F-18]Me4FDG may enable improvement in glycemic control in diabetes by PET-based monitoring strategies.
en-copyright=
kn-copyright=

en-aut-name=MatsusakaYohji
en-aut-sei=Matsusaka
en-aut-mei=Yohji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=ChenXinyu
en-aut-sei=Chen
en-aut-mei=Xinyu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=Arias-LozaPaula
en-aut-sei=Arias-Loza
en-aut-mei=Paula
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=WernerRudolf A.
en-aut-sei=Werner
en-aut-mei=Rudolf A.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=NoseNaoko
en-aut-sei=Nose
en-aut-mei=Naoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=SasakiTakanori
en-aut-sei=Sasaki
en-aut-mei=Takanori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=RoweSteven P.
en-aut-sei=Rowe
en-aut-mei=Steven P.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=PomperMartin G.
en-aut-sei=Pomper
en-aut-mei=Martin G.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=LapaConstantin
en-aut-sei=Lapa
en-aut-mei=Constantin
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=HiguchiTakahiro
en-aut-sei=Higuchi
en-aut-mei=Takahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

affil-num=1
en-affil=Department of Nuclear Medicine and Comprehensive Heart Failure Center, University Hospital of Würzburg
kn-affil=

affil-num=2
en-affil=Department of Nuclear Medicine and Comprehensive Heart Failure Center, University Hospital of Würzburg
kn-affil=

affil-num=3
en-affil=Department of Nuclear Medicine and Comprehensive Heart Failure Center, University Hospital of Würzburg
kn-affil=

affil-num=4
en-affil=Department of Nuclear Medicine and Comprehensive Heart Failure Center, University Hospital of Würzburg
kn-affil=

affil-num=5
en-affil=Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=6
en-affil=Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=7
en-affil=Division of Nuclear Medicine and Molecular Imaging, The Russell H Morgan Department of Radiology and Radiological Sciences, Johns Hopkins School of Medicine
kn-affil=

affil-num=8
en-affil=Division of Nuclear Medicine and Molecular Imaging, The Russell H Morgan Department of Radiology and Radiological Sciences, Johns Hopkins School of Medicine
kn-affil=

affil-num=9
en-affil= Nuclear Medicine, Faculty of Medicine, University of Augsburg
kn-affil=

affil-num=10
en-affil=Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
END

start-ver=1.4
cd-journal=joma
no-vol=12
cd-vols=
no-issue=1
article-no=
start-page=18787
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20221105
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Generative adversarial network-created brain SPECTs of cerebral ischemia are indistinguishable to scans from real patients
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Deep convolutional generative adversarial networks (GAN) allow for creating images from existing databases. We applied a modified light-weight GAN (FastGAN) algorithm to cerebral blood flow SPECTs and aimed to evaluate whether this technology can generate created images close to real patients. Investigating three anatomical levels (cerebellum, CER; basal ganglia, BG; cortex, COR), 551 normal (248 CER, 174 BG, 129 COR) and 387 pathological brain SPECTs using N-isopropyl p-I-123-iodoamphetamine (I-123-IMP) were included. For the latter scans, cerebral ischemic disease comprised 291 uni- (66 CER, 116 BG, 109 COR) and 96 bilateral defect patterns (44 BG, 52 COR). Our model was trained using a three-compartment anatomical input (dataset 'A'; including CER, BG, and COR), while for dataset 'B', only one anatomical region (COR) was included. Quantitative analyses provided mean counts (MC) and left/right (LR) hemisphere ratios, which were then compared to quantification from real images. For MC, 'B' was significantly different for normal and bilateral defect patterns (P < 0.0001, respectively), but not for unilateral ischemia (P = 0.77). Comparable results were recorded for LR, as normal and ischemia scans were significantly different relative to images acquired from real patients (P <= 0.01, respectively). Images provided by 'A', however, revealed comparable quantitative results when compared to real images, including normal (P = 0.8) and pathological scans (unilateral, P = 0.99; bilateral, P = 0.68) for MC. For LR, only uni- (P = 0.03), but not normal or bilateral defect scans (P >= 0.08) reached significance relative to images of real patients. With a minimum of only three anatomical compartments serving as stimuli, created cerebral SPECTs are indistinguishable to images from real patients. The applied FastGAN algorithm may allow to provide sufficient scan numbers in various clinical scenarios, e.g., for "data-hungry" deep learning technologies or in the context of orphan diseases.
en-copyright=
kn-copyright=

en-aut-name=WernerRudolf A.
en-aut-sei=Werner
en-aut-mei=Rudolf A.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=HiguchiTakahiro
en-aut-sei=Higuchi
en-aut-mei=Takahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=NoseNaoko
en-aut-sei=Nose
en-aut-mei=Naoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=ToriumiFujio
en-aut-sei=Toriumi
en-aut-mei=Fujio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=MatsusakaYohji
en-aut-sei=Matsusaka
en-aut-mei=Yohji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=KujiIchiei
en-aut-sei=Kuji
en-aut-mei=Ichiei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=KazuhiroKoshino
en-aut-sei=Kazuhiro
en-aut-mei=Koshino
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

affil-num=1
en-affil=Department of Nuclear Medicine, University Hospital Würzburg
kn-affil=

affil-num=2
en-affil=Graduate School of  Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=3
en-affil=Graduate School of  Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=4
en-affil=Department of Systems  Innovation, Graduate School of Engineering, The University of Tokyo
kn-affil=

affil-num=5
en-affil=Department of Nuclear Medicine, University Hospital Würzburg
kn-affil=

affil-num=6
en-affil=Department of Nuclear  Medicine, Saitama Medical University International Medical Center
kn-affil=

affil-num=7
en-affil=Department of Systems and  Informatics, Hokkaido Information University
kn-affil=
END

start-ver=1.4
cd-journal=joma
no-vol=2021
cd-vols=
no-issue=
article-no=
start-page=4629459
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=20211206
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=The Number of Frames on ECG-Gated F-18-FDG Small Animal PET Has a Significant Impact on LV Systolic and Diastolic Functional Parameters
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Objectives. This study is aimed at investigating the impact of frame numbers in preclinical electrocardiogram- (ECG-) gated F-18-fluorodeoxyglucose (F-18-FDG) positron emission tomography (PET) on systolic and diastolic left ventricular (LV) parameters in rats. Methods. F-18-FDG PET imaging using a dedicated small animal PET system with list mode data acquisition and continuous ECG recording was performed in diabetic and control rats. The list-mode data was sorted and reconstructed with different numbers of frames (4, 8, 12, and 16) per cardiac cycle into tomographic images. Using an automatic ventricular edge detection software, left ventricular (LV) functional parameters, including ejection fraction (EF), end-diastolic (EDV), and end-systolic volume (ESV), were calculated. Diastolic variables (time to peak filling (TPF), first third mean filling rate (1/3 FR), and peak filling rate (PFR)) were also assessed. Results. Significant differences in multiple parameters were observed among the reconstructions with different frames per cardiac cycle. EDV significantly increased by numbers of frames (353.8 & PLUSMN; 57.7 mu l*, 380.8 & PLUSMN; 57.2 mu l*, 398.0 & PLUSMN; 63.1 mu l*, and 444.8 & PLUSMN; 75.3 mu l at 4, 8, 12, and 16 frames, respectively; *P < 0.0001 vs. 16 frames), while systolic (EF) and diastolic (TPF, 1/3 FR and PFR) parameters were not significantly different between 12 and 16 frames. In addition, significant differences between diabetic and control animals in 1/3 FR and PFR in 16 frames per cardiac cycle were observed (P < 0.005), but not for 4, 8, and 12 frames. Conclusions. Using ECG-gated PET in rats, measurements of cardiac function are significantly affected by the frames per cardiac cycle. Therefore, if you are going to compare those functional parameters, a consistent number of frames should be used.
en-copyright=
kn-copyright=

en-aut-name=EisslerChristoph
en-aut-sei=Eissler
en-aut-mei=Christoph
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=WernerRudolf A.
en-aut-sei=Werner
en-aut-mei=Rudolf A.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=Arias-LozaPaula
en-aut-sei=Arias-Loza
en-aut-mei=Paula
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=NoseNaoko
en-aut-sei=Nose
en-aut-mei=Naoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=ChenXinyu
en-aut-sei=Chen
en-aut-mei=Xinyu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=PomperMartin G.
en-aut-sei=Pomper
en-aut-mei=Martin G.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=RoweSteven P.
en-aut-sei=Rowe
en-aut-mei=Steven P.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=LapaConstantin
en-aut-sei=Lapa
en-aut-mei=Constantin
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=BuckAndreas K.
en-aut-sei=Buck
en-aut-mei=Andreas K.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=HiguchiTakahiro
en-aut-sei=Higuchi
en-aut-mei=Takahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

affil-num=1
en-affil=Department of Nuclear Medicine, University Hospital Würzburg
kn-affil=

affil-num=2
en-affil=Department of Nuclear Medicine, University Hospital Würzburg
kn-affil=

affil-num=3
en-affil=Department of Nuclear Medicine, University Hospital Würzburg
kn-affil=

affil-num=4
en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=5
en-affil=Department of Nuclear Medicine, University Hospital Würzburg
kn-affil=

affil-num=6
en-affil=The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine
kn-affil=

affil-num=7
en-affil=The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine
kn-affil=

affil-num=8
en-affil=Department of Nuclear Medicine, University Hospital Augsburg
kn-affil=

affil-num=9
en-affil=Department of Nuclear Medicine, University Hospital Würzburg
kn-affil=

affil-num=10
en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
END

start-ver=1.4
cd-journal=joma
no-vol=11
cd-vols=
no-issue=1
article-no=
start-page=10896
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=20210525
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=[18F]FDG-labelled stem cell PET imaging in different route of administrations and multiple animal species
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Stem cell therapy holds great promise for tissue regeneration and cancer treatment, although its efficacy is still inconclusive and requires further understanding and optimization of the procedures. Non-invasive cell tracking can provide an important opportunity to monitor in vivo cell distribution in living subjects. Here, using a combination of positron emission tomography (PET) and in vitro 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) direct cell labelling, the feasibility of engrafted stem cell monitoring was tested in multiple animal species. Human mesenchymal stem cells (MSCs) were incubated with phosphate-buffered saline containing [18F]FDG for in vitro cell radiolabelling. The pre-labelled MSCs were administrated via peripheral vein in a mouse (n=1), rats (n=4), rabbits (n=4) and non-human primates (n=3), via carotid artery in rats (n=4) and non-human primates (n=3), and via intra-myocardial injection in rats (n=5). PET imaging was started 10 min after cell administration using a dedicated small animal PET system for a mouse and rats. A clinical PET system was used for the imaging of rabbits and non-human primates. After MSC administration via peripheral vein, PET imaging revealed intense radiotracer signal from the lung in all tested animal species including mouse, rat, rabbit, and non-human primate, suggesting administrated MSCs were trapped in the lung tissue. Furthermore, the distribution of the PET signal significantly differed based on the route of cell administration. Administration via carotid artery showed the highest activity in the head, and intra-myocardial injection increased signal from the heart. In vitro [18F]FDG MSC pre-labelling for PET imaging is feasible and allows non-invasive visualization of initial cell distribution after different routes of cell administration in multiple animal models. Those results highlight the potential use of that imaging approach for the understanding and optimization of stem cell therapy in translational research.
en-copyright=
kn-copyright=

en-aut-name=NoseNaoko
en-aut-sei=Nose
en-aut-mei=Naoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=NogamiSuguru
en-aut-sei=Nogami
en-aut-mei=Suguru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KoshinoKazuhiro
en-aut-sei=Koshino
en-aut-mei=Kazuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=ChenXinyu
en-aut-sei=Chen
en-aut-mei=Xinyu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=WernerRudolf A.
en-aut-sei=Werner
en-aut-mei=Rudolf A.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=KashimaSoki
en-aut-sei=Kashima
en-aut-mei=Soki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=RoweSteven P.
en-aut-sei=Rowe
en-aut-mei=Steven P.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=LapaConstantin
en-aut-sei=Lapa
en-aut-mei=Constantin
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=FukuchiKazuki
en-aut-sei=Fukuchi
en-aut-mei=Kazuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=HiguchiTakahiro
en-aut-sei=Higuchi
en-aut-mei=Takahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

affil-num=1
en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=2
en-affil=Department of Medical Physics and Engineering, Division of Health Sciences, Osaka University Graduate School of Medicine
kn-affil=

affil-num=3
en-affil=Department of Systems and Informatics, Hokkaido Information University
kn-affil=

affil-num=4
en-affil=Comprehensive Heart Failure Center and Department of Nuclear Medicine, University Hospital Würzburg
kn-affil=

affil-num=5
en-affil=Comprehensive Heart Failure Center and Department of Nuclear Medicine, University Hospital Würzburg
kn-affil=

affil-num=6
en-affil=Department of Urology, Akita University Graduate School of Medicine
kn-affil=

affil-num=7
en-affil=The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine
kn-affil=

affil-num=8
en-affil=Nuclear Medicine, Medical Faculty, University of Augsburg
kn-affil=

affil-num=9
en-affil=Department of Medical Physics and Engineering, Division of Health Sciences, Osaka University Graduate School of Medicine
kn-affil=

affil-num=10
en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
END

start-ver=1.4
cd-journal=joma
no-vol=11
cd-vols=
no-issue=12
article-no=
start-page=6105
end-page=6119
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=20210407
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Current and future perspectives on functional molecular imaging in nephro-urology: theranostics on the horizon
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=In recent years, a paradigm shift from single-photon-emitting radionuclide radiotracers toward positron-emission tomography (PET) radiotracers has occurred in nuclear oncology. Although PET-based molecular imaging of the kidneys is still in its infancy, such a trend has emerged in the field of functional renal radionuclide imaging. Potentially allowing for precise and thorough evaluation of renal radiotracer urodynamics, PET radionuclide imaging has numerous advantages including precise anatomical co-registration with CT images and dynamic three-dimensional imaging capability. In addition, relative to scintigraphic approaches, PET can allow for significantly reduced scan time enabling high-throughput in a busy PET practice and further reduces radiation exposure, which may have a clinical impact in pediatric populations. In recent years, multiple renal PET radiotracers labeled with C-11, Ga-68, and F-18 have been utilized in clinical studies. Beyond providing a precise non-invasive read-out of renal function, such radiotracers may also be used to assess renal inflammation. This manuscript will provide an overview of renal molecular PET imaging and will highlight the transformation of conventional scintigraphy of the kidneys toward novel, high-resolution PET imaging for assessing renal function. In addition, future applications will be introduced, e.g. by transferring the concept of molecular image-guided diagnostics and therapy (theranostics) to the field of nephrology.
en-copyright=
kn-copyright=

en-aut-name=ToyamaYoshitaka
en-aut-sei=Toyama
en-aut-mei=Yoshitaka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=WernerRudolf A.
en-aut-sei=Werner
en-aut-mei=Rudolf A.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=Ruiz-BedoyaCamilo A.
en-aut-sei=Ruiz-Bedoya
en-aut-mei=Camilo A.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=OrdonezAlvaro A.
en-aut-sei=Ordonez
en-aut-mei=Alvaro A.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=TakaseKei
en-aut-sei=Takase
en-aut-mei=Kei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=LapaConstantin
en-aut-sei=Lapa
en-aut-mei=Constantin
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=JainSanjay K.
en-aut-sei=Jain
en-aut-mei=Sanjay K.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=PomperMartin G.
en-aut-sei=Pomper
en-aut-mei=Martin G.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=RoweSteven P.
en-aut-sei=Rowe
en-aut-mei=Steven P.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=HiguchiTakahiro
en-aut-sei=Higuchi
en-aut-mei=Takahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

affil-num=1
en-affil=Department of Nuclear Medicine, University Hospital Wuerzburg
kn-affil=

affil-num=2
en-affil=Department of Nuclear Medicine, University Hospital Wuerzburg
kn-affil=

affil-num=3
en-affil=Center for Infection and Inflammation Imaging Research, Johns Hopkins University School of Medicine
kn-affil=

affil-num=4
en-affil=Center for Infection and Inflammation Imaging Research, Johns Hopkins University School of Medicine
kn-affil=

affil-num=5
en-affil=Department of Diagnostic Radiology, Tohoku University
kn-affil=

affil-num=6
en-affil=Nuclear Medicine, Medical Faculty, University of Augsburg
kn-affil=

affil-num=7
en-affil=Center for Infection and Inflammation Imaging Research, Johns Hopkins University School of Medicine
kn-affil=

affil-num=8
en-affil=Division of Nuclear Medicine and Molecular Imaging, The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine
kn-affil=

affil-num=9
en-affil=Division of Nuclear Medicine and Molecular Imaging, The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine
kn-affil=

affil-num=10
en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=Glomerular filtration rate
kn-keyword=Glomerular filtration rate
en-keyword=renal
kn-keyword=renal
en-keyword=kidney
kn-keyword=kidney
en-keyword=renal function
kn-keyword=renal function
en-keyword=positron emission tomography
kn-keyword=positron emission tomography
en-keyword=nephrology
kn-keyword=nephrology
en-keyword=urology
kn-keyword=urology
en-keyword=molecular imaging
kn-keyword=molecular imaging
en-keyword=theranostics
kn-keyword=theranostics
END

start-ver=1.4
cd-journal=joma
no-vol=46
cd-vols=
no-issue=9
article-no=
start-page=1773
end-page=1786
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2019
dt-pub=20190530
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=The next era of renal radionuclide imaging: novel PET radiotracers
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Although single-photon-emitting radiotracers have long been the standard for renal functional molecular imaging, recent years have seen the development of positron emission tomography (PET) agents for this application. We provide an overview of renal radionuclide PET radiotracers, in particular focusing on novel 18F-labelled and 68Ga-labelled agents. Several reported PET imaging probes allow assessment of glomerular filtration rate, such as [68Ga]ethylenediaminetetraacetic acid ([68Ga]EDTA), [68Ga]IRDye800-tilmanocept and 2-deoxy-2-[18F]fluorosorbitol ([18F]FDS)). The diagnostic performance of [68Ga]EDTA has already been demonstrated in a clinical trial. [68Ga]IRDye800-tilmanocept shows receptor-mediated binding to glomerular mesangial cells, which in turn may allow the monitoring of progression of diabetic nephropathy. [18F]FDS shows excellent kidney extraction and excretion in rats and, as has been shown in the first study in humans. Further, due to its simple one-step radiosynthesis via the most frequently used PET radiotracer 2-deoxy-2-[18F]fluoro-d-glucose, [18F]FDS could be available at nearly every PET centre. A new PET radiotracer has also been introduced for the effective assessment of plasma flow in the kidneys: Re(CO)3-N-([18F]fluoroethyl)iminodiacetic acid (Re(CO)3([18F]FEDA)). This compound demonstrates similar pharmacokinetic properties to its 99mTc-labelled analogue [99mTc](CO)3(FEDA). Thus, if there is a shortage of molybdenum-99, Re(CO)3([18F]FEDA would allow direct comparison with previous studies with 99mTc. The PET radiotracers for renal imaging reviewed here allow thorough evaluation of kidney function, with the tremendous advantage of precise anatomical coregistration with simultaneously acquired CT images and rapid three-dimensional imaging capability.
en-copyright=
kn-copyright=

en-aut-name=WernerRudolf A.
en-aut-sei=Werner
en-aut-mei=Rudolf A.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=ChenXinyu
en-aut-sei=Chen
en-aut-mei=Xinyu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=LapaConstantin
en-aut-sei=Lapa
en-aut-mei=Constantin
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=KoshinoKazuhiro
en-aut-sei=Koshino
en-aut-mei=Kazuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=RoweSteven P.
en-aut-sei=Rowe
en-aut-mei=Steven P.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=PomperMartin G.
en-aut-sei=Pomper
en-aut-mei=Martin G.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=JavadiMehrbod S.
en-aut-sei=Javadi
en-aut-mei=Mehrbod S.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=HiguchiTakahiro
en-aut-sei=Higuchi
en-aut-mei=Takahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

affil-num=1
en-affil=Department of Nuclear Medicine/Comprehensive Heart Failure Center, University of Wuerzburg
kn-affil=

affil-num=2
en-affil=Department of Nuclear Medicine/Comprehensive Heart Failure Center, University of Wuerzburg
kn-affil=

affil-num=3
en-affil=Department of Nuclear Medicine/Comprehensive Heart Failure Center, University of Wuerzburg
kn-affil=

affil-num=4
en-affil=Department of Biomedical Imaging, National Cardiovascular and Cerebral Center
kn-affil=

affil-num=5
en-affil=Division of Nuclear Medicine and Molecular Imaging, The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine
kn-affil=

affil-num=6
en-affil=
kn-affil=

affil-num=7
en-affil=Division of Nuclear Medicine and Molecular Imaging, The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine
kn-affil=

affil-num=8
en-affil=Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School
kn-affil=
en-keyword=Kidney
kn-keyword=Kidney
en-keyword=Positron emission tomography
kn-keyword=Positron emission tomography
en-keyword=PET
kn-keyword=PET
en-keyword=[18F]Fluorodeoxysorbitol
kn-keyword=[18F]Fluorodeoxysorbitol
en-keyword=GFR
kn-keyword=GFR
en-keyword=ERPF
kn-keyword=ERPF
END

start-ver=1.4
cd-journal=joma
no-vol=22
cd-vols=
no-issue=3
article-no=
start-page=602
end-page=611
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2019
dt-pub=20190722
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Initial Evaluation of AF78: a Rationally Designed Fluorine-18-Labelled PET Radiotracer Targeting Norepinephrine Transporter
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Purpose</br>
Taking full advantage of positron emission tomography (PET) technology, fluorine-18-labelled radiotracers targeting norepinephrine transporter (NET) have potential applications in the diagnosis and assessment of cardiac sympathetic nerve conditions as well as the delineation of neuroendocrine tumours. However, to date, none have been used clinically. Drawbacks of currently reported radiotracers include suboptimal kinetics and challenging radiolabelling procedures.</br>
Procedures</br>
We developed a novel fluorine-18-labelled radiotracer targeting NET, AF78, with efficient one-step radiolabelling based on the phenethylguanidine structure. Radiosynthesis of AF78 was undertaken, followed by validation in cell uptake studies, autoradiography, and in vivo imaging in rats.</br>
Results</br>
[18F]AF78 was successfully synthesized with 27.9 ± 3.1 % radiochemical yield, > 97 % radiochemical purity and > 53.8 GBq/mmol molar activity. Cell uptake studies demonstrated essentially identical affinity for NET as norepinephrine and meta-iodobenzylgaunidine. Both ex vivo autoradiography and in vivo imaging in rats showed homogeneous and specific cardiac uptake.</br>
Conclusions</br>
The new PET radiotracer [18F]AF78 demonstrated high affinity for NET and favourable biodistribution in rats. A structure-activity relationship between radiotracer structures and affinity for NET was revealed, which may serve as the basis for the further design of NET targeting radiotracers with favourable features.
en-copyright=
kn-copyright=

en-aut-name=ChenXinyu
en-aut-sei=Chen
en-aut-mei=Xinyu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=FritzAlexander
en-aut-sei=Fritz
en-aut-mei=Alexander
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=WernerRudolf A.
en-aut-sei=Werner
en-aut-mei=Rudolf A.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=NoseNaoko
en-aut-sei=Nose
en-aut-mei=Naoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=YagiYusuke
en-aut-sei=Yagi
en-aut-mei=Yusuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=KimuraHiroyuki
en-aut-sei=Kimura
en-aut-mei=Hiroyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=RoweSteven P.
en-aut-sei=Rowe
en-aut-mei=Steven P.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=KoshinoKazuhiro
en-aut-sei=Koshino
en-aut-mei=Kazuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=DeckerMichael
en-aut-sei=Decker
en-aut-mei=Michael
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=HiguchiTakahiro
en-aut-sei=Higuchi
en-aut-mei=Takahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

affil-num=1
en-affil=Department of Nuclear Medicine, University Hospital of Würzburg
kn-affil=

affil-num=2
en-affil=Institute of Pharmacy and Food Chemistry, University of Würzburg
kn-affil=

affil-num=3
en-affil=Department of Nuclear Medicine, University Hospital of Würzburg
kn-affil=

affil-num=4
en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=5
en-affil=Department of Analytical and Bioinorganic Chemistry, Division of Analytical and Physical Sciences, Kyoto Pharmaceutical University
kn-affil=

affil-num=6
en-affil=Department of Analytical and Bioinorganic Chemistry, Division of Analytical and Physical Sciences, Kyoto Pharmaceutical University
kn-affil=

affil-num=7
en-affil=Division of Nuclear Medicine and Molecular Imaging, Russel H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine
kn-affil=

affil-num=8
en-affil=Department of Systems and Informatics, Hokkaido Information University
kn-affil=

affil-num=9
en-affil=Institute of Pharmacy and Food Chemistry, University of Würzburg
kn-affil=

affil-num=10
en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=Norepinephrine transporter
kn-keyword=Norepinephrine transporter
en-keyword=Positron emission tomography
kn-keyword=Positron emission tomography
en-keyword=Phenethylguanidine
kn-keyword=Phenethylguanidine
en-keyword=[18F]AF78
kn-keyword=[18F]AF78
END

start-ver=1.4
cd-journal=joma
no-vol=127
cd-vols=
no-issue=6
article-no=
start-page=851
end-page=873
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2020
dt-pub=20200409
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Recent advances in radiotracers targeting norepinephrine transporter: structural development and radiolabeling improvements
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=The norepinephrine transporter (NET) is a major target for the evaluation of the cardiac sympathetic nerve system in patients with heart failure and Parkinson's disease. It is also used in the therapeutic applications against certain types of neuroendocrine tumors, as exemplified by the clinically used 123/131I-MIBG as theranostic single-photon emission computed tomography (SPECT) agent. With the development of more advanced positron emission tomography (PET) technology, more radiotracers targeting NET have been reported, with superior temporal and spatial resolutions, along with the possibility of functional and kinetic analysis. More recently, fluorine-18-labelled NET tracers have drawn increasing attentions from researchers, due to their longer radiological half-life relative to carbon-11 (110 min vs. 20 min), reduced dependence on on-site cyclotrons, and flexibility in the design of novel tracer structures. In the heart, certain NET tracers provide integral diagnostic information on sympathetic innervation and the nerve status. In the central nervous system, such radiotracers can reveal NET distribution and density in pathological conditions. Most radiotracers targeting cardiac NET-function for the cardiac application consistent of derivatives of either norepinephrine or MIBG with its benzylguanidine core structure, e.g. 11C-HED and 18F-LMI1195. In contrast, all NET tracers used in central nervous system applications are derived from clinically used antidepressants. Lastly, possible applications of NET as selective tracers over organic cation transporters (OCTs) in the kidneys and other organs controlled by sympathetic nervous system will also be discussed.
en-copyright=
kn-copyright=

en-aut-name=ChenXinyu
en-aut-sei=Chen
en-aut-mei=Xinyu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KudoTakashi
en-aut-sei=Kudo
en-aut-mei=Takashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=LapaConstantin
en-aut-sei=Lapa
en-aut-mei=Constantin
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=BuckAndreas
en-aut-sei=Buck
en-aut-mei=Andreas
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=HiguchiTakahiro
en-aut-sei=Higuchi
en-aut-mei=Takahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

affil-num=1
en-affil=Department of Nuclear Medicine, University Hospital of Würzburg
kn-affil=

affil-num=2
en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=3
en-affil=Department of Nuclear Medicine, University Hospital of Würzburg
kn-affil=

affil-num=4
en-affil=Department of Nuclear Medicine, University Hospital of Würzburg
kn-affil=

affil-num=5
en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=Norepinephrine transporter
kn-keyword=Norepinephrine transporter
en-keyword=Benzylguanidine
kn-keyword=Benzylguanidine
en-keyword=Phenethylguanidine
kn-keyword=Phenethylguanidine
en-keyword=Antidepressant
kn-keyword=Antidepressant
en-keyword=Organic cation transporter
kn-keyword=Organic cation transporter
END

start-ver=1.4
cd-journal=joma
no-vol=10
cd-vols=
no-issue=1
article-no=
start-page=18616
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2020
dt-pub=20201029
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Capabilities of multi-pinhole SPECT with two stationary detectors for in vivo rat imaging
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=We aimed to investigate the image quality of the U-SPECT5/CT E-Class a micro single-photon emission computed tomography (SPECT) system with two large stationary detectors for visualization of rat hearts and bones using clinically available Tc-99m-labelled tracers. Sensitivity, spatial resolution, uniformity and contrast-to-noise ratio (CNR) of the small-animal SPECT scanner were investigated in phantom studies using an ultra-high-resolution rat and mouse multi-pinhole collimator (UHR-RM). Point source, hot-rod, and uniform phantoms with Tc-99m-solution were scanned for high-count performance assessment and count levels equal to animal scans, respectively. Reconstruction was performed using the similarity-regulated ordered-subsets expectation maximization (SROSEM) algorithm with Gaussian smoothing. Rats were injected with similar to 100 MBq [Tc-99m]Tc-MIBI or similar to 150 MBq [Tc-99m]Tc-HMDP and received multi-frame micro-SPECT imaging after tracer distribution. Animal scans were reconstructed for three different acquisition times and post-processed with different sized Gaussian filters. Following reconstruction, CNR was calculated and image quality evaluated by three independent readers on a five-point scale from 1="very poor" to 5="very good". Point source sensitivity was 567 cps/MBq and radioactive rods as small as 1.2 mm were resolved with the UHR-RM collimator. Collimator-dependent uniformity was 55.5%. Phantom CNR improved with increasing rod size, filter size and activity concentration. Left ventricle and bone structures were successfully visualized in rat experiments. Image quality was strongly affected by the extent of post-filtering, whereas scan time did not have substantial influence on visual assessment. Good image quality was achieved for resolution range greater than 1.8 mm in bone and 2.8 mm in heart. The recently introduced small animal SPECT system with two stationary detectors and UHR-RM collimator is capable to provide excellent image quality in heart and bone scans in a rat using standardized reconstruction parameters and appropriate post-filtering. However, there are still challenges in achieving maximum system resolution in the sub-millimeter range with in vivo settings under limited injection dose and acquisition time.
en-copyright=
kn-copyright=

en-aut-name=JanssenJan P.
en-aut-sei=Janssen
en-aut-mei=Jan P.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=HoffmannJan V.
en-aut-sei=Hoffmann
en-aut-mei=Jan V.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KannoTakayuki
en-aut-sei=Kanno
en-aut-mei=Takayuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=NoseNaoko
en-aut-sei=Nose
en-aut-mei=Naoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=GrunzJan-Peter
en-aut-sei=Grunz
en-aut-mei=Jan-Peter
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=OnoguchiMasahisa
en-aut-sei=Onoguchi
en-aut-mei=Masahisa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=ChenXinyu
en-aut-sei=Chen
en-aut-mei=Xinyu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=LapaConstantin
en-aut-sei=Lapa
en-aut-mei=Constantin
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=BuckAndreas K.
en-aut-sei=Buck
en-aut-mei=Andreas K.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=HiguchiTakahiro
en-aut-sei=Higuchi
en-aut-mei=Takahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

affil-num=1
en-affil=Department of Nuclear Medicine, University Hospital Würzburg
kn-affil=

affil-num=2
en-affil=Department of Nuclear Medicine, University Hospital Würzburg
kn-affil=

affil-num=3
en-affil=Comprehensive Heart Failure Centre, University Hospital Würzburg
kn-affil=

affil-num=4
en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=5
en-affil=Department of Diagnostic and Interventional Radiology, University Hospital Würzburg
kn-affil=

affil-num=6
en-affil=Department of Quantum Medical Technology, Graduate School of Medical Sciences, Kanazawa University
kn-affil=

affil-num=7
en-affil=Comprehensive Heart Failure Centre, University Hospital Würzburg
kn-affil=

affil-num=8
en-affil=Nuclear Medicine, Medical Faculty, University of Augsburg
kn-affil=

affil-num=9
en-affil=Department of Nuclear Medicine, University Hospital Würzburg
kn-affil=

affil-num=10
en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=Biomarkers
kn-keyword=Biomarkers
en-keyword=Diagnostic markers
kn-keyword=Diagnostic markers
en-keyword=Medical research
kn-keyword=Medical research
en-keyword=Preclinical research
kn-keyword=Preclinical research
en-keyword=Translational research
kn-keyword=Translational research
END

start-ver=1.4
cd-journal=joma
no-vol=7
cd-vols=
no-issue=1
article-no=
start-page=64
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2020
dt-pub=20201102
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Performance evaluation of fifth-generation ultra-high-resolution SPECT system with two stationary detectors and multi-pinhole imaging
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background Small-animal single-photon emission computed tomography (SPECT) systems with multi-pinhole collimation and large stationary detectors have advantages compared to systems with moving small detectors. These systems benefit from less labour-intensive maintenance and quality control as fewer prone parts are moving, higher accuracy for focused scans and maintaining high resolution with increased sensitivity due to focused pinholes on the field of view. This study aims to investigate the performance of a novel ultra-high-resolution scanner with two-detector configuration (U-SPECT5-E) and to compare its image quality to a conventional micro-SPECT system with three stationary detectors (U-SPECT+). Methods The new U-SPECT5-E with two stationary detectors was used for acquiring data with Tc-99m-filled point source, hot-rod and uniformity phantoms to analyse sensitivity, spatial resolution, uniformity and contrast-to-noise ratio (CNR). Three dedicated multi-pinhole mouse collimators with 75 pinholes each and 0.25-, 0.60- and 1.00-mm pinholes for extra ultra-high resolution (XUHR-M), general-purpose (GP-M) and ultra-high sensitivity (UHS-M) imaging were examined. For CNR analysis, four different activity ranges representing low- and high-count settings were investigated for all three collimators. The experiments for the performance assessment were repeated with the same GP-M collimator in the three-detector U-SPECT+ for comparison. Results Peak sensitivity was 237 cps/MBq (XUHR-M), 847 cps/MBq (GP-M), 2054 cps/MBq (UHS-M) for U-SPECT5-E and 1710 cps/MBq (GP-M) for U-SPECT+. In the visually analysed sections of the reconstructed mini Derenzo phantoms, rods as small as 0.35 mm (XUHR-M), 0.50 mm (GP-M) for the two-detector as well as the three-detector SPECT and 0.75 mm (UHS-M) were resolved. Uniformity for maximum resolution recorded 40.7% (XUHR-M), 29.1% (GP-M, U-SPECT5-E), 16.3% (GP-M, U-SPECT+) and 23.0% (UHS-M), respectively. UHS-M reached highest CNR values for low-count images; for rods smaller than 0.45 mm, acceptable CNR was only achieved by XUHR-M. GP-M was superior for imaging rods sized from 0.60 to 1.50 mm for intermediate activity concentrations. U-SPECT5-E and U-SPECT+ both provided comparable CNR. Conclusions While uniformity and sensitivity are negatively affected by the absence of a third detector, the investigated U-SPECT5-E system with two stationary detectors delivers excellent spatial resolution and CNR comparable to the performance of an established three-detector-setup.
en-copyright=
kn-copyright=

en-aut-name=HoffmannJan, V
en-aut-sei=Hoffmann
en-aut-mei=Jan, V
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=JanssenJan P.
en-aut-sei=Janssen
en-aut-mei=Jan P.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KannoTakayuki
en-aut-sei=Kanno
en-aut-mei=Takayuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=ShibutaniTakayuki
en-aut-sei=Shibutani
en-aut-mei=Takayuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=OnoguchiMasahisa
en-aut-sei=Onoguchi
en-aut-mei=Masahisa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=LapaConstantin
en-aut-sei=Lapa
en-aut-mei=Constantin
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=GrunzJan-Peter
en-aut-sei=Grunz
en-aut-mei=Jan-Peter
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=BuckAndreas K.
en-aut-sei=Buck
en-aut-mei=Andreas K.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=HiguchiTakahiro
en-aut-sei=Higuchi
en-aut-mei=Takahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

affil-num=1
en-affil=Department of Nuclear Medicine, University Hospital Würzburg
kn-affil=

affil-num=2
en-affil=Department of Nuclear Medicine, University Hospital Würzburg
kn-affil=

affil-num=3
en-affil=Comprehensive Heart Failure Center, University Hospital Würzburg
kn-affil=

affil-num=4
en-affil=Department of Quantum Medical Technology, Graduate School of Medical Sciences
kn-affil=

affil-num=5
en-affil=Department of Quantum Medical Technology, Graduate School of Medical Sciences
kn-affil=

affil-num=6
en-affil=Nuclear Medicine, Medical Faculty, University of Augsburg
kn-affil=

affil-num=7
en-affil=Department of Diagnostic and Interventional Radiology, University Hospital Würzburg
kn-affil=

affil-num=8
en-affil=Department of Nuclear Medicine, University Hospital Würzburg
kn-affil=

affil-num=9
en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=Small-animal imaging
kn-keyword=Small-animal imaging
en-keyword=SPECT
kn-keyword=SPECT
en-keyword=Mouse
kn-keyword=Mouse
en-keyword=Collimator
kn-keyword=Collimator
en-keyword=Post-reconstruction filtering
kn-keyword=Post-reconstruction filtering
END

start-ver=1.4
cd-journal=joma
no-vol=23
cd-vols=
no-issue=4
article-no=
start-page=100998
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2020
dt-pub=20200424
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Cytotoxic T Lymphocytes Regenerated from iPS Cells Have Therapeutic Efficacy in a Patient-Derived Xenograft Solid Tumor Model
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Current adoptive T cell therapies conducted in an autologous setting are costly, time consuming, and depend on the quality of the patient's T cells. To address these issues, we developed a strategy in which cytotoxic T lymphocytes (CTLs) are regenerated from iPSCs that were originally derived from T cells and succeeded in regenerating CTLs specific for the WT1 antigen, which exhibited therapeutic efficacy in a xenograft model of leukemia. In this study, we extended our strategy to solid tumors. The regenerated WT1-specific CTLs had a strong therapeutic effect in orthotopic xenograft model using a renal cell carcinoma (RCC) cell line. To make our method more generally applicable, we developed an allogeneic approach by transducing HLA-haplotype homozygous iPSCs with WT1-specific TCR α/β genes that had been tested clinically. The regenerated CTLs antigen-specifically suppressed tumor growth in a patient-derived xenograft model of RCC, demonstrating the feasibility of our strategy against solid tumors. 
en-copyright=
kn-copyright=

en-aut-name=KashimaSoki
en-aut-sei=Kashima
en-aut-mei=Soki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=MaedaTakuya
en-aut-sei=Maeda
en-aut-mei=Takuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=MasudaKyoko
en-aut-sei=Masuda
en-aut-mei=Kyoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=NaganoSeiji
en-aut-sei=Nagano
en-aut-mei=Seiji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=InoueTakamitsu
en-aut-sei=Inoue
en-aut-mei=Takamitsu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=TakedaMasashi
en-aut-sei=Takeda
en-aut-mei=Masashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=KonoYuka
en-aut-sei=Kono
en-aut-mei=Yuka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=KobayashiTakashi
en-aut-sei=Kobayashi
en-aut-mei=Takashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=SaitoShigeyoshi
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ORCID=

en-aut-name=HiguchiTakahiro
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aut-affil-num=10
ORCID=

en-aut-name=Ichise Hiroshi
en-aut-sei=Ichise
en-aut-mei= Hiroshi
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kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=KobayashiYuka
en-aut-sei=Kobayashi
en-aut-mei=Yuka
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aut-affil-num=12
ORCID=

en-aut-name=IwaisakoKeiko
en-aut-sei=Iwaisako
en-aut-mei=Keiko
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kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=TeradaKoji
en-aut-sei=Terada
en-aut-mei=Koji
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kn-aut-sei=
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aut-affil-num=14
ORCID=

en-aut-name=AgataYasutoshi
en-aut-sei=Agata
en-aut-mei=Yasutoshi
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kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=

en-aut-name=NumakuraKazuyuki
en-aut-sei=Numakura
en-aut-mei=Kazuyuki
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kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=

en-aut-name=SaitoMitsuru
en-aut-sei=Saito
en-aut-mei=Mitsuru
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kn-aut-mei=
aut-affil-num=17
ORCID=

en-aut-name=NaritaShintaro
en-aut-sei=Narita
en-aut-mei=Shintaro
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kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=

en-aut-name=YasukawaMasaki
en-aut-sei=Yasukawa
en-aut-mei=Masaki
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kn-aut-sei=
kn-aut-mei=
aut-affil-num=19
ORCID=

en-aut-name=OgawaOsamu
en-aut-sei=Ogawa
en-aut-mei=Osamu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=20
ORCID=

en-aut-name=HabuchiTomonori
en-aut-sei=Habuchi
en-aut-mei=Tomonori
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kn-aut-sei=
kn-aut-mei=
aut-affil-num=21
ORCID=

en-aut-name=KawamotoHiroshi
en-aut-sei=Kawamoto
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=22
ORCID=

affil-num=1
en-affil=Laboratory of Immunology, Institute for Frontier Life and Medical Sciences, Kyoto University
kn-affil=

affil-num=2
en-affil=Laboratory of Immunology, Institute for Frontier Life and Medical Sciences, Kyoto University
kn-affil=

affil-num=3
en-affil=Laboratory of Immunology, Institute for Frontier Life and Medical Sciences, Kyoto University
kn-affil=

affil-num=4
en-affil=Laboratory of Immunology, Institute for Frontier Life and Medical Sciences, Kyoto University
kn-affil=

affil-num=5
en-affil= Department of Urology, Akita University Graduate School of Medicine
kn-affil=

affil-num=6
en-affil=Department of Urology, Kyoto University Graduate School of Medicine
kn-affil=

affil-num=7
en-affil= Laboratory of Immunology, Institute for Frontier Life and Medical Sciences, Kyoto University
kn-affil=

affil-num=8
en-affil=Department of Urology, Kyoto University Graduate School of Medicine
kn-affil=

affil-num=9
en-affil=Department of Medical Physics and Engineering, Division of Health Sciences, Osaka University
kn-affil=

affil-num=10
en-affil=Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=

affil-num=11
en-affil=Laboratory of Immunology, Institute for Frontier Life and Medical Sciences, Kyoto University
kn-affil=

affil-num=12
en-affil=Laboratory of Immunology, Institute for Frontier Life and Medical Sciences, Kyoto University
kn-affil=

affil-num=13
en-affil=Department of Medical Life Systems, Faculty of Life and Medical Sciences, Doshisha University
kn-affil=

affil-num=14
en-affil=Department of Biochemistry and Molecular Biology, Shiga University of Medical School
kn-affil=

affil-num=15
en-affil=Department of Biochemistry and Molecular Biology, Shiga University of Medical School
kn-affil=

affil-num=16
en-affil=Department of Urology, Akita University Graduate School of Medicine
kn-affil=

affil-num=17
en-affil=Department of Urology, Akita University Graduate School of Medicine
kn-affil=

affil-num=18
en-affil=Department of Urology, Akita University Graduate School of Medicine
kn-affil=

affil-num=19
en-affil=Department of Hematology, Clinical Immunology and Infectious Diseases, Graduate School of Medicine, Ehime University
kn-affil=

affil-num=20
en-affil=Department of Urology, Kyoto University Graduate School of Medicine
kn-affil=

affil-num=21
en-affil=Department of Urology, Akita University Graduate School of Medicine
kn-affil=

affil-num=22
en-affil= Laboratory of Immunology, Institute for Frontier Life and Medical Sciences, Kyoto University
kn-affil=
en-keyword=Cancer
kn-keyword=Cancer
en-keyword=Cellular Therapy
kn-keyword=Cellular Therapy
en-keyword=Immunological Methods
kn-keyword=Immunological Methods
END

start-ver=1.4
cd-journal=joma
no-vol=9
cd-vols=
no-issue=
article-no=
start-page=17026
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2019
dt-pub=20191119
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Ventricular Distribution Pattern of the Novel Sympathetic Nerve PET Radiotracer F-18-LMI1195 in Rabbit Hearts
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=We aimed to determine a detailed regional ventricular distribution pattern of the novel cardiac nerve PET radiotracer F-18-LMI1195 in healthy rabbits. Ex-vivo high resolution autoradiographic imaging was conducted to identify accurate ventricular distribution of F-18-LMI1195. In healthy rabbits, F-18-LMI1195 was administered followed by the reference perfusion marker Tl-201 for a dual-radiotracer analysis. After 20 min of F-18-LMI1195 distribution time, the rabbits were euthanized, the hearts were extracted, frozen, and cut into 20-mu m short axis slices. Subsequently, the short axis sections were exposed to a phosphor imaging plate to determine F-18-LMI1195 distribution (exposure for 3 h). After complete F-18 decay, sections were re-exposed to determine Tl-201 distribution (exposure for 7 days). For quantitative analysis, segmental regions of Interest (ROIs) were divided into four left ventricular (LV) and a right ventricular (RV) segment on mid-ventricular short axis sections. Subendocardial, midportion, and subepicardial ROIs were placed on the LV lateral wall. F-18-LMI1195 distribution was almost homogeneous throughout the LV wall without any significant differences in all four LV ROIs (anterior, posterior, septal and lateral wall, 99 +/- 2, 94 +/- 5, 94 +/- 4 and 97 +/- 3%LV, respectively, n.s.). Subepicardial Tl-201 uptake was significantly lower compared to the subendocardial portion (subendocardial, midportion, and subepicardial activity: 90 +/- 3, 96 +/- 2 and *80 +/- 5%LV, respectively, *p < 0.01 vs. midportion). This was in contradistinction to the transmural wall profile of F-18-LMI1195 (90 +/- 4, 96 +/- 5 and 84 +/- 4%LV, n.s.). A slight but significant discrepant transmural radiotracer distribution pattern of Tl-201 in comparison to F-18-LMI1195 may be a reflection of physiological sympathetic innervation and perfusion in rabbit hearts.
en-copyright=
kn-copyright=

en-aut-name=WernerRudolf A.
en-aut-sei=Werner
en-aut-mei=Rudolf A.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=WakabayashiHiroshi
en-aut-sei=Wakabayashi
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=ChenXinyu
en-aut-sei=Chen
en-aut-mei=Xinyu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=HayakawaNobuyuki
en-aut-sei=Hayakawa
en-aut-mei=Nobuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=LapaConstantin
en-aut-sei=Lapa
en-aut-mei=Constantin
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kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=RoweSteven P.
en-aut-sei=Rowe
en-aut-mei=Steven P.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=JavadiMehrbod S.
en-aut-sei=Javadi
en-aut-mei=Mehrbod S.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=RobinsonSimon
en-aut-sei=Robinson
en-aut-mei=Simon
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aut-affil-num=8
ORCID=

en-aut-name=HiguchiTakahiro
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kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

affil-num=1
en-affil=The Russell H. Morgan Department of Radiology and Radiological Science, Division of Nuclear Medicine and Molecular Imaging, Johns Hopkins School University of Medicine
kn-affil=

affil-num=2
en-affil= Department of Nuclear Medicine, Hannover Medical School
kn-affil=

affil-num=3
en-affil= Department of Nuclear Medicine, Hannover Medical School
kn-affil=

affil-num=4
en-affil= Department of Nuclear Medicine, Hannover Medical School
kn-affil=

affil-num=5
en-affil=Department of Nuclear Medicine, University Hospital, University of Würzburg
kn-affil=

affil-num=6
en-affil=The Russell H. Morgan Department of Radiology and Radiological Science, Division of Nuclear Medicine and Molecular Imaging, Johns Hopkins School University of Medicine
kn-affil=

affil-num=7
en-affil=The Russell H. Morgan Department of Radiology and Radiological Science, Division of Nuclear Medicine and Molecular Imaging, Johns Hopkins School University of Medicine
kn-affil=

affil-num=8
en-affil= Lantheus Medical Imaging
kn-affil=

affil-num=9
en-affil=Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
END