Sangeeta Ray Banerjee1,2, Vivek Kumar3, Ala Lisok3, Jian Chen3, Il Minn3, Mary Brummet3, Srikanth Boinapally3, Michael Cole3, Ethel Ngen3, Bryan Wharram3, Cory Brayton4, Robert F Hobbs3, Martin G Pomper5,6. 1. Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA. sray9@jhmi.edu. 2. Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA. sray9@jhmi.edu. 3. Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA. 4. Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. 5. Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA. mpomper@jhmi.edu. 6. Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA. mpomper@jhmi.edu.
Abstract
PURPOSE: To develop a prostate-specific membrane antigen (PSMA)-targeted radiotherapeutic for metastatic castration-resistant prostate cancer (mCRPC) with optimized efficacy and minimized toxicity employing the β-particle radiation of 177Lu. METHODS: We synthesized 14 new PSMA-targeted, 177Lu-labeled radioligands (177Lu-L1-177Lu-L14) using different chelating agents and linkers. We evaluated them in vitro using human prostate cancer PSMA(+) PC3 PIP and PSMA(-) PC3 flu cells and in corresponding flank tumor models. Efficacy and toxicity after 8 weeks were evaluated at a single administration of 111 MBq for 177Lu-L1, 177Lu-L3, 177Lu-L5 and 177Lu-PSMA-617. Efficacy of 177Lu-L1 was further investigated using different doses, and long-term toxicity was determined in healthy immunocompetent mice. RESULTS: Radioligands were produced in high radiochemical yield and purity. Cell uptake and internalization indicated specific uptake only in PSMA(+) PC3 cells. 177Lu-L1, 177Lu-L3 and 177Lu-L5 demonstrated comparable uptake to 177Lu-PSMA-617 and 177Lu-PSMA-I&T in PSMA-expressing tumors up to 72 h post-injection. 177Lu-L1, 177Lu-L3 and 177Lu-L5 also demonstrated efficient tumor regression at 8 weeks. 177Lu-L1 enabled the highest survival rate. Necropsy studies of the treated group at 8 weeks revealed subacute damage to lacrimal glands and testes. No radiation nephropathy was observed 1 year post-treatment in healthy mice receiving 111 MBq of 177Lu-L1, most likely related to the fast renal clearance of this agent. CONCLUSIONS: 177Lu-L1 is a viable clinical candidate for radionuclide therapy of PSMA-expressing malignancies because of its high tumor-targeting ability and low off-target radiotoxic effects.
PURPOSE: To develop a prostate-specific membrane antigen (PSMA)-targeted radiotherapeutic for metastatic castration-resistant prostate cancer (mCRPC) with optimized efficacy and minimized toxicity employing the β-particle radiation of 177Lu. METHODS: We synthesized 14 new PSMA-targeted, 177Lu-labeled radioligands (177Lu-L1-177Lu-L14) using different chelating agents and linkers. We evaluated them in vitro using humanprostate cancerPSMA(+) PC3PIP and PSMA(-) PC3 flu cells and in corresponding flank tumor models. Efficacy and toxicity after 8 weeks were evaluated at a single administration of 111 MBq for 177Lu-L1, 177Lu-L3, 177Lu-L5 and 177Lu-PSMA-617. Efficacy of 177Lu-L1 was further investigated using different doses, and long-term toxicity was determined in healthy immunocompetent mice. RESULTS: Radioligands were produced in high radiochemical yield and purity. Cell uptake and internalization indicated specific uptake only in PSMA(+) PC3 cells. 177Lu-L1, 177Lu-L3 and 177Lu-L5 demonstrated comparable uptake to 177Lu-PSMA-617 and 177Lu-PSMA-I&T in PSMA-expressing tumors up to 72 h post-injection. 177Lu-L1, 177Lu-L3 and 177Lu-L5 also demonstrated efficient tumor regression at 8 weeks. 177Lu-L1 enabled the highest survival rate. Necropsy studies of the treated group at 8 weeks revealed subacute damage to lacrimal glands and testes. No radiation nephropathy was observed 1 year post-treatment in healthy mice receiving 111 MBq of 177Lu-L1, most likely related to the fast renal clearance of this agent. CONCLUSIONS:177Lu-L1 is a viable clinical candidate for radionuclide therapy of PSMA-expressing malignancies because of its high tumor-targeting ability and low off-target radiotoxic effects.
Authors: Lionel G Bouchet; Wesley E Bolch; H Pablo Blanco; Barry W Wessels; Jeffry A Siegel; Didier A Rajon; Isabelle Clairand; George Sgouros Journal: J Nucl Med Date: 2003-07 Impact factor: 10.057
Authors: Sangeeta Ray Banerjee; Catherine A Foss; Mrudula Pullambhatla; Yuchuan Wang; Senthamizhchelvan Srinivasan; Robert F Hobbs; Kwamena E Baidoo; Martin W Brechbiel; Sridhar Nimmagadda; Ronnie C Mease; George Sgouros; Martin G Pomper Journal: J Nucl Med Date: 2015-02-26 Impact factor: 10.057
Authors: Clemens Kratochwil; Frank Bruchertseifer; Hendrik Rathke; Marcus Bronzel; Christos Apostolidis; Wilko Weichert; Uwe Haberkorn; Frederik L Giesel; Alfred Morgenstern Journal: J Nucl Med Date: 2017-04-13 Impact factor: 10.057
Authors: Wolfgang P Fendler; Kambiz Rahbar; Ken Herrmann; Clemens Kratochwil; Matthias Eiber Journal: J Nucl Med Date: 2017-06-29 Impact factor: 10.057
Authors: Sangeeta Ray Banerjee; Zhengping Chen; Mrudula Pullambhatla; Ala Lisok; Jian Chen; Ronnie C Mease; Martin G Pomper Journal: Bioconjug Chem Date: 2016-05-09 Impact factor: 4.774
Authors: Wolfgang P Fendler; Andreea D Stuparu; Susan Evans-Axelsson; Katharina Lückerath; Liu Wei; Woosuk Kim; Soumya Poddar; Jonathan Said; Caius G Radu; Matthias Eiber; Johannes Czernin; Roger Slavik; Ken Herrmann Journal: J Nucl Med Date: 2017-05-25 Impact factor: 10.057
Authors: Sangeeta R Banerjee; Catherine A Foss; Mark Castanares; Ronnie C Mease; Youngjoo Byun; James J Fox; John Hilton; Shawn E Lupold; Alan P Kozikowski; Martin G Pomper Journal: J Med Chem Date: 2008-07-19 Impact factor: 7.446
Authors: Kambiz Rahbar; Ali Afshar-Oromieh; Robert Seifert; Stefan Wagner; Michael Schäfers; Martin Bögemann; Matthias Weckesser Journal: Eur J Nucl Med Mol Imaging Date: 2018-07-20 Impact factor: 9.236
Authors: Srikanth Boinapally; Alla Lisok; Gabriela Lofland; Il Minn; Yu Yan; Zirui Jiang; Min Jay Shin; Vanessa F Merino; Lei Zheng; Cory Brayton; Martin G Pomper; Sangeeta Ray Banerjee Journal: Eur J Nucl Med Mol Imaging Date: 2022-08-15 Impact factor: 10.057
Authors: Ronnie C Mease; Choong Mo Kang; Vivek Kumar; Sangeeta Ray Banerjee; Il Minn; Mary Brummet; Kathleen L Gabrielson; Yutian Feng; Andrew Park; Ana P Kiess; George Sgouros; Ganesan Vaidyanathan; Michael R Zalutsky; Martin G Pomper Journal: J Nucl Med Date: 2021-06-04 Impact factor: 10.057
Authors: Ganesan Vaidyanathan; Ronnie C Mease; Il Minn; Jaeyeon Choi; Ying Chen; Hassan Shallal; Choong Mo Kang; Darryl McDougald; Vivek Kumar; Martin G Pomper; Michael R Zalutsky Journal: Nucl Med Biol Date: 2021-01-23 Impact factor: 2.408
Authors: Sangeeta Ray Banerjee; Il Minn; Vivek Kumar; Anders Josefsson; Ala Lisok; Mary Brummet; Jian Chen; Ana P Kiess; Kwamena Baidoo; Cory Brayton; Ronnie C Mease; Martin Brechbiel; George Sgouros; Robert F Hobbs; Martin G Pomper Journal: J Nucl Med Date: 2019-06-28 Impact factor: 11.082
Authors: Ethel J Ngen; Ying Chen; Babak Behnam Azad; Srikanth Boinapally; Desmond Jacob; Ala Lisok; Chentian Shen; Mir S Hossain; Jiefu Jin; Zaver M Bhujwalla; Martin G Pomper; Sangeeta R Banerjee Journal: Nanotheranostics Date: 2021-01-19
Authors: Sangeeta Ray Banerjee; Ala Lisok; Il Minn; Anders Josefsson; Vivek Kumar; Mary Brummet; Srikanth Boinapally; Cory Brayton; Ronnie C Mease; George Sgouros; Robert F Hobbs; Martin G Pomper Journal: J Nucl Med Date: 2020-11-27 Impact factor: 10.057