PURPOSE: Prostate-specific membrane antigen (PSMA) is a cell surface protein that is overexpressed in prostate cancer, including hormone-refractory and metastatic disease. Our goal in this study was to develop a series of PSMA-based imaging agents for clinical use. EXPERIMENTAL DESIGN: We have synthesized and evaluated the in vivo biodistribution of two radiolabeled urea derivatives that have high affinity for PSMA in severe combined immunodeficient mice harboring MCF-7 (breast, PSMA-negative), PC-3 (prostate, PSMA-negative), and LNCaP (prostate, PSMA-positive) xenografts. Radiopharmaceutical binding selectivity and tumor uptake were also evaluated in vivo using dedicated small animal positron emission tomography, single photon emission computed tomography, and gamma scintigraphic imaging devices. N-[N-[(S)-1,3-dicarboxypropyl]carbamoyl]-S-[(11)C]methyl-L-cysteine ([(11)C]DCMC K(i), 3.1 nmol/L) and N-[N-[(S)-1,3-dicarboxypropyl]carbamoyl]-S-3-[(125)I]iodo-L-tyrosine ([(125)C]DCIT K(i), 1.5 nmol/L) were synthesized using [(11)C]CH(3)I and with [(125)I]NaI/Iodogen, respectively. RESULTS: At 30 minutes postinjection, [(11)C]DCMC and [(125)I]DCIT showed tumor/muscle ratios of 10.8 and 4.7, respectively, with clear delineation of LNCaP-derived tumors on imaging. MCF-7- and PC-3-derived tumors showed significantly less uptake of [(11)C]DCMC or [(125)I]DCIT. CONCLUSION: These results show the feasibility of imaging PSMA-positive prostate cancer using low molecular weight agents.
PURPOSE: Prostate-specific membrane antigen (PSMA) is a cell surface protein that is overexpressed in prostate cancer, including hormone-refractory and metastatic disease. Our goal in this study was to develop a series of PSMA-based imaging agents for clinical use. EXPERIMENTAL DESIGN: We have synthesized and evaluated the in vivo biodistribution of two radiolabeled urea derivatives that have high affinity for PSMA in severe combined immunodeficientmice harboring MCF-7 (breast, PSMA-negative), PC-3 (prostate, PSMA-negative), and LNCaP (prostate, PSMA-positive) xenografts. Radiopharmaceutical binding selectivity and tumor uptake were also evaluated in vivo using dedicated small animal positron emission tomography, single photon emission computed tomography, and gamma scintigraphic imaging devices. N-[N-[(S)-1,3-dicarboxypropyl]carbamoyl]-S-[(11)C]methyl-L-cysteine ([(11)C]DCMC K(i), 3.1 nmol/L) and N-[N-[(S)-1,3-dicarboxypropyl]carbamoyl]-S-3-[(125)I]iodo-L-tyrosine ([(125)C]DCIT K(i), 1.5 nmol/L) were synthesized using [(11)C]CH(3)I and with [(125)I]NaI/Iodogen, respectively. RESULTS: At 30 minutes postinjection, [(11)C]DCMC and [(125)I]DCIT showed tumor/muscle ratios of 10.8 and 4.7, respectively, with clear delineation of LNCaP-derived tumors on imaging. MCF-7- and PC-3-derived tumors showed significantly less uptake of [(11)C]DCMC or [(125)I]DCIT. CONCLUSION: These results show the feasibility of imaging PSMA-positive prostate cancer using low molecular weight agents.
Authors: Ying Chen; Mrudula Pullambhatla; Catherine A Foss; Youngjoo Byun; Sridhar Nimmagadda; Srinivasan Senthamizhchelvan; George Sgouros; Ronnie C Mease; Martin G Pomper Journal: Clin Cancer Res Date: 2011-10-31 Impact factor: 12.531
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: Ying Chen; Catherine A Foss; Youngjoo Byun; Sridhar Nimmagadda; Mrudula Pullambhatla; James J Fox; Mark Castanares; Shawn E Lupold; John W Babich; Ronnie C Mease; Martin G Pomper Journal: J Med Chem Date: 2008-12-25 Impact factor: 7.446
Authors: Andrei Fodor; Andrea Lancia; Francesco Ceci; Maria Picchio; Morten Hoyer; Barbara Alicja Jereczek-Fossa; Piet Ost; Paolo Castellucci; Elena Incerti; Nadia Di Muzio; Gianluca Ingrosso Journal: World J Urol Date: 2018-05-11 Impact factor: 4.226
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