UNLABELLED: This phase 1 study was performed to determine the pharmacokinetics and ability to visualize prostate cancer in bone, soft-tissue, and the prostate gland using (123)I-MIP-1072 and (123)I-MIP-1095, novel radiolabeled small molecules targeting prostate-specific membrane antigen. METHODS: Seven patients with a documented history of prostate cancer by histopathology or radiologic evidence of metastatic disease were intravenously administered 370 MBq (10 mCi) of (123)I-MIP-1072 and (123)I-MIP-1095 2 wk apart in a crossover trial design. (123)I-MIP-1072 was also studied in 6 healthy volunteers. Whole-body planar and SPECT/CT imaging was performed and pharmacokinetics studied over 2-3 d. Target-to-background ratios were calculated. Absorbed radiation doses were estimated using OLINDA/EXM. RESULTS: (123)I-MIP-1072 and (123)I-MIP-1095 visualized lesions in soft tissue, bone, and the prostate gland within 0.5-1 h after injection, with retention beyond 48 h. Target-to-background ratios from planar images averaged 2:1 at 1 h, 3:1 at 4-24 h, and greater than 10:1 at 4 and 24 h for SPECT/CT. Both agents cleared the blood in a biphasic manner; clearance of (123)I-MIP-1072 was approximately 5 times faster. (123)I-MIP-1072 was excreted in the urine, with 54% and 74% present by 24 and 72 h, respectively. In contrast, only 7% and 20% of (123)I-MIP-1095 had been renally excreted by 24 and 72 h, respectively. Estimated absorbed radiation doses were 0.054 versus 0.110 mGy/MBq for the kidneys and 0.024 versus 0.058 mGy/MBq for the liver, for (123)I-MIP-1072 and (123)I-MIP-1095, respectively. CONCLUSION: (123)I-MIP-1072 and (123)I-MIP-1095 detect lesions in soft tissue, bone, and the prostate gland at as early as 1-4 h. These novel radiolabeled small molecules have excellent pharmacokinetic and pharmacodynamic profiles and warrant further development as diagnostic and potentially when labeled with (131)I therapeutic radiopharmaceuticals.
UNLABELLED: This phase 1 study was performed to determine the pharmacokinetics and ability to visualize prostate cancer in bone, soft-tissue, and the prostate gland using (123)I-MIP-1072 and (123)I-MIP-1095, novel radiolabeled small molecules targeting prostate-specific membrane antigen. METHODS: Seven patients with a documented history of prostate cancer by histopathology or radiologic evidence of metastatic disease were intravenously administered 370 MBq (10 mCi) of (123)I-MIP-1072 and (123)I-MIP-1095 2 wk apart in a crossover trial design. (123)I-MIP-1072 was also studied in 6 healthy volunteers. Whole-body planar and SPECT/CT imaging was performed and pharmacokinetics studied over 2-3 d. Target-to-background ratios were calculated. Absorbed radiation doses were estimated using OLINDA/EXM. RESULTS: (123)I-MIP-1072 and (123)I-MIP-1095 visualized lesions in soft tissue, bone, and the prostate gland within 0.5-1 h after injection, with retention beyond 48 h. Target-to-background ratios from planar images averaged 2:1 at 1 h, 3:1 at 4-24 h, and greater than 10:1 at 4 and 24 h for SPECT/CT. Both agents cleared the blood in a biphasic manner; clearance of (123)I-MIP-1072 was approximately 5 times faster. (123)I-MIP-1072 was excreted in the urine, with 54% and 74% present by 24 and 72 h, respectively. In contrast, only 7% and 20% of (123)I-MIP-1095 had been renally excreted by 24 and 72 h, respectively. Estimated absorbed radiation doses were 0.054 versus 0.110 mGy/MBq for the kidneys and 0.024 versus 0.058 mGy/MBq for the liver, for (123)I-MIP-1072 and (123)I-MIP-1095, respectively. CONCLUSION: (123)I-MIP-1072 and (123)I-MIP-1095 detect lesions in soft tissue, bone, and the prostate gland at as early as 1-4 h. These novel radiolabeled small molecules have excellent pharmacokinetic and pharmacodynamic profiles and warrant further development as diagnostic and potentially when labeled with (131)I therapeutic radiopharmaceuticals.
Authors: Xing Yang; Ronnie C Mease; Mrudula Pullambhatla; Ala Lisok; Ying Chen; Catherine A Foss; Yuchuan Wang; Hassan Shallal; Hannah Edelman; Adam T Hoye; Giorgio Attardo; Sridhar Nimmagadda; Martin G Pomper Journal: J Med Chem Date: 2015-12-16 Impact factor: 7.446
Authors: Ali Afshar-Oromieh; Uwe Haberkorn; Boris Hadaschik; Gregor Habl; Matthias Eder; Michael Eisenhut; Heinz-Peter Schlemmer; Matthias C Roethke Journal: Eur J Nucl Med Mol Imaging Date: 2013-07-02 Impact factor: 9.236
Authors: Xinning Wang; Steve S Huang; Warren D W Heston; Hong Guo; Bing-Cheng Wang; James P Basilion Journal: Mol Cancer Ther Date: 2014-09-19 Impact factor: 6.261
Authors: Steven P Rowe; Alexander Drzezga; Bernd Neumaier; Markus Dietlein; Michael A Gorin; Michael R Zalutsky; Martin G Pomper Journal: J Nucl Med Date: 2016-10 Impact factor: 10.057
Authors: Steven P Rowe; Katarzyna J Macura; Anthony Ciarallo; Esther Mena; Amanda Blackford; Rosa Nadal; Emmanuel S Antonarakis; Mario A Eisenberger; Michael A Carducci; Ashley E Ross; Philip W Kantoff; Daniel P Holt; Robert F Dannals; Ronnie C Mease; Martin G Pomper; Steve Y Cho Journal: J Nucl Med Date: 2015-10-22 Impact factor: 10.057
Authors: Christian M Zechmann; Ali Afshar-Oromieh; Tom Armor; James B Stubbs; Walter Mier; Boris Hadaschik; John Joyal; Klaus Kopka; Jürgen Debus; John W Babich; Uwe Haberkorn Journal: Eur J Nucl Med Mol Imaging Date: 2014-02-28 Impact factor: 9.236