TY - JOUR
T1 - Preclinical comparative study of 68Ga-labeled DOTA, NOTA, and HBED-CC chelated radiotracers for targeting PSMA
AU - Ray Banerjee, Sangeeta
AU - Chen, Zhengping
AU - Pullambhatla, Mrudula
AU - Lisok, Ala
AU - Chen, Jian
AU - Mease, Ronnie C.
AU - Pomper, Martin G.
N1 - Funding Information:
We are grateful to NIH K25 CA148901, U54 CA151838, R01 CA134675, R01 CA184228, U01 CA183031, and the Patrick Walsh Foundation for Prostate Cancer Research. We thank the JHU PET Center for access to the 68Ga generator. We would like to thank Gilbert Green and Desmond Jacob for their assistant with imaging studies. Dr. Zhengping Chen would like to thank Jiangsu Government Scholarship for Overseas Studies (JS-2011-054) and The Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Institute of Nuclear Medicine, P.R. China, for his fellowship. Dr. Jian Chen would like to thank China Scholarship Council and Key Laboratory of Smart Drug Delivery, Ministry of Education and Fudan University, Shanghai, P.R. China, for his fellowship.
Publisher Copyright:
© 2016 American Chemical Society.
PY - 2016/6/15
Y1 - 2016/6/15
N2 - 68Ga-labeled, low-molecular-weight imaging agents that target the prostate-specific membrane antigen (PSMA) are increasingly used clinically to detect prostate and other cancers with positron emission tomography (PET). The goal of this study was to compare the pharmacokinetics of three PSMA-targeted radiotracers: 68Ga-1, using DOTA-monoamide as the chelating agent; 68Ga-2, containing the macrocyclic chelating agent p-SCN-Bn-NOTA; and 68Ga-DKFZ-PSMA-11, currently in clinical trials, which uses the acyclic chelating agent, HBED-CC. The PSMA-targeting scaffold for all three agents utilized a similar Glu-urea-Lys-linker construct. Each radiotracer enabled visualization of PSMA+ PC3 PIP tumor, kidney, and urinary bladder as early as 15 min post-injection using small animal PET/computed tomography (PET/CT). 68Ga-2 demonstrated the fastest rate of clearance from all tissues in this series and displayed higher uptake in PSMA+ PC3 PIP tumor compared to 68Ga-1 at 1 h post-injection. There was no significant difference in PSMA+ PC3 PIP tumor uptake for the three agents at 2 and 3 h post-injection. 68Ga-DKFZ-PSMA-11 demonstrated the highest uptake and retention in normal tissues, including kidney, blood, spleen, and salivary glands and PSMA-negative PC3 flu tumors up to 3 h post-injection. In this preclinical evaluation 68Ga-2 had the most advantageous characteristics for PSMA-targeted PET imaging.
AB - 68Ga-labeled, low-molecular-weight imaging agents that target the prostate-specific membrane antigen (PSMA) are increasingly used clinically to detect prostate and other cancers with positron emission tomography (PET). The goal of this study was to compare the pharmacokinetics of three PSMA-targeted radiotracers: 68Ga-1, using DOTA-monoamide as the chelating agent; 68Ga-2, containing the macrocyclic chelating agent p-SCN-Bn-NOTA; and 68Ga-DKFZ-PSMA-11, currently in clinical trials, which uses the acyclic chelating agent, HBED-CC. The PSMA-targeting scaffold for all three agents utilized a similar Glu-urea-Lys-linker construct. Each radiotracer enabled visualization of PSMA+ PC3 PIP tumor, kidney, and urinary bladder as early as 15 min post-injection using small animal PET/computed tomography (PET/CT). 68Ga-2 demonstrated the fastest rate of clearance from all tissues in this series and displayed higher uptake in PSMA+ PC3 PIP tumor compared to 68Ga-1 at 1 h post-injection. There was no significant difference in PSMA+ PC3 PIP tumor uptake for the three agents at 2 and 3 h post-injection. 68Ga-DKFZ-PSMA-11 demonstrated the highest uptake and retention in normal tissues, including kidney, blood, spleen, and salivary glands and PSMA-negative PC3 flu tumors up to 3 h post-injection. In this preclinical evaluation 68Ga-2 had the most advantageous characteristics for PSMA-targeted PET imaging.
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U2 - 10.1021/acs.bioconjchem.5b00679
DO - 10.1021/acs.bioconjchem.5b00679
M3 - Article
C2 - 27076393
AN - SCOPUS:84975166630
VL - 27
SP - 1447
EP - 1455
JO - Bioconjugate Chemistry
JF - Bioconjugate Chemistry
SN - 1043-1802
IS - 6
ER -