Neeta Pandit-Taskar1,2, Joseph A O'Donoghue3, Shutian Ruan4, Serge K Lyashchenko5, Jorge A Carrasquillo4,2, Glenn Heller6, Danny F Martinez7, Sarah M Cheal8, Jason S Lewis4,2,5,8, Martin Fleisher9, Jennifer S Keppler10, Robert E Reiter10, Anna M Wu10, Wolfgang A Weber4,2, Howard I Scher7,11, Steven M Larson4,2,8, Michael J Morris7,11. 1. Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York pandit-n@mskcc.org. 2. Department of Radiology, Weill Cornell Medical College, New York, New York. 3. Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York. 4. Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York. 5. Radiochemistry and Molecular Imaging Probes Core, Memorial Sloan Kettering Cancer Center, New York, New York. 6. Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York. 7. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York. 8. Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, New York. 9. Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York. 10. ImaginAb, Inc., Inglewood, California; and. 11. Department of Medicine, Weill Cornell Medical College, New York, New York.
Abstract
We conducted a phase I dose-escalation study with 89Zr-desferrioxamine-IAB2M (89Zr-IAB2M), an anti-prostate-specific membrane antigen minibody, in patients with metastatic prostate cancer. METHODS: Patients received 185 MBq (5 mCi) of 89Zr-IAB2M and Df-IAB2M at total mass doses of 10 (n = 6), 20 (n = 6), and 50 mg (n = 6). Whole-body and serum clearance, normal-organ and lesion uptake, and radiation absorbed dose were estimated, and the effect of mass escalation was analyzed. RESULTS: Eighteen patients were injected and scanned without side effects. Whole-body clearance was monoexponential, with a median biologic half-life of 215 h, whereas serum clearance showed biexponential kinetics, with a median biologic half-life of 3.7 (12.3%/L) and 33.8 h (17.9%/L). The radiation absorbed dose estimates were 1.67, 1.36, and 0.32 mGy/MBq to liver, kidney, and marrow, respectively, with an effective dose of 0.41 mSv/MBq (1.5 rem/mCi). Both skeletal and nodal lesions were detected with 89Zr-IAB2M, most visualized by 48-h imaging. CONCLUSION: 89Zr-IAB2M is safe and demonstrates favorable biodistribution and kinetics for targeting metastatic prostate cancer. Imaging with 10 mg of minibody mass provides optimal biodistribution, and imaging at 48 h after injection provides good lesion visualization. Assessment of lesion targeting is being studied in detail in an expansion cohort.
We conducted a phase I dose-escalation study with 89Zr-desferrioxamine-IAB2M (89Zr-IAB2M), an anti-prostate-specific membrane antigen minibody, in patients with metastatic prostate cancer. METHODS:Patients received 185 MBq (5 mCi) of 89Zr-IAB2M and Df-IAB2M at total mass doses of 10 (n = 6), 20 (n = 6), and 50 mg (n = 6). Whole-body and serum clearance, normal-organ and lesion uptake, and radiation absorbed dose were estimated, and the effect of mass escalation was analyzed. RESULTS: Eighteen patients were injected and scanned without side effects. Whole-body clearance was monoexponential, with a median biologic half-life of 215 h, whereas serum clearance showed biexponential kinetics, with a median biologic half-life of 3.7 (12.3%/L) and 33.8 h (17.9%/L). The radiation absorbed dose estimates were 1.67, 1.36, and 0.32 mGy/MBq to liver, kidney, and marrow, respectively, with an effective dose of 0.41 mSv/MBq (1.5 rem/mCi). Both skeletal and nodal lesions were detected with 89Zr-IAB2M, most visualized by 48-h imaging. CONCLUSION: 89Zr-IAB2M is safe and demonstrates favorable biodistribution and kinetics for targeting metastatic prostate cancer. Imaging with 10 mg of minibody mass provides optimal biodistribution, and imaging at 48 h after injection provides good lesion visualization. Assessment of lesion targeting is being studied in detail in an expansion cohort.
Authors: Neeta Pandit-Taskar; Joseph A O'Donoghue; Volkan Beylergil; Serge Lyashchenko; Shutian Ruan; Stephen B Solomon; Jeremy C Durack; Jorge A Carrasquillo; Robert A Lefkowitz; Mithat Gonen; Jason S Lewis; Jason P Holland; Sarah M Cheal; Victor E Reuter; Joseph R Osborne; Massimo F Loda; Peter M Smith-Jones; Wolfgang A Weber; Neil H Bander; Howard I Scher; Michael J Morris; Steven M Larson Journal: Eur J Nucl Med Mol Imaging Date: 2014-08-21 Impact factor: 9.236
Authors: Maria J W D Vosjan; Lars R Perk; Gerard W M Visser; Marianne Budde; Paul Jurek; Garry E Kiefer; Guus A M S van Dongen Journal: Nat Protoc Date: 2010-03-25 Impact factor: 13.491
Authors: Neil H Bander; Matthew I Milowsky; David M Nanus; Lale Kostakoglu; Shankar Vallabhajosula; Stanley J Goldsmith Journal: J Clin Oncol Date: 2005-04-18 Impact factor: 44.544
Authors: Jason P Holland; Vadim Divilov; Neil H Bander; Peter M Smith-Jones; Steven M Larson; Jason S Lewis Journal: J Nucl Med Date: 2010-07-21 Impact factor: 10.057
Authors: Tove Olafsen; David Betting; Vania E Kenanova; Felix B Salazar; Pat Clarke; Jonathan Said; Andrew A Raubitschek; John M Timmerman; Anna M Wu Journal: J Nucl Med Date: 2009-08-18 Impact factor: 10.057
Authors: Uwe Schauer; Frank Stemberg; Christian H L Rieger; Michael Borte; Simone Schubert; Frank Riedel; Udo Herz; Harald Renz; Manfred Wick; Hugh D Carr-Smith; Arthur R Bradwell; Wilhelm Herzog Journal: Clin Chem Date: 2003-11 Impact factor: 8.327
Authors: Jeffrey V Leyton; Tove Olafsen; Eric J Lepin; Scott Hahm; Karl B Bauer; Robert E Reiter; Anna M Wu Journal: Clin Cancer Res Date: 2008-11-15 Impact factor: 12.531
Authors: Andrea K Miyahira; Joshua M Lang; Robert B Den; Isla P Garraway; Tamara L Lotan; Ashley E Ross; Tanya Stoyanova; Steve Y Cho; Jonathan W Simons; Kenneth J Pienta; Howard R Soule Journal: Prostate Date: 2015-10-19 Impact factor: 4.104
Authors: Joseph A O'Donoghue; Jason S Lewis; Neeta Pandit-Taskar; Stephen E Fleming; Heiko Schöder; Steven M Larson; Volkan Beylergil; Shutian Ruan; Serge K Lyashchenko; Pat B Zanzonico; Wolfgang A Weber; Jorge A Carrasquillo; Yelena Y Janjigian Journal: J Nucl Med Date: 2017-06-21 Impact factor: 10.057
Authors: Joseph R Osborne; Teja M Kalidindi; Blesida J Punzalan; Kishore Gangangari; Daniel E Spratt; Wolfgang A Weber; Steven M Larson; Naga Vara Kishore Pillarsetty Journal: Mol Imaging Biol Date: 2017-12 Impact factor: 3.488
Authors: Anthony F Shields; Paula M Jacobs; Mario Sznol; Michael M Graham; Ron N Germain; Lawrence G Lum; Elizabeth M Jaffee; Elisabeth G E de Vries; Sridhar Nimmagadda; Annick D Van den Abbeele; David K Leung; Anna M Wu; Elad Sharon; Lalitha K Shankar Journal: J Nucl Med Date: 2017-08-17 Impact factor: 10.057
Authors: Francois H Cornelis; Jeremy C Durack; Neeta Pandit-Taskar; Gary A Ulaner; Jason S Lewis; Michael J Morris; Stephen B Solomon Journal: J Nucl Med Date: 2017-08-17 Impact factor: 10.057
Authors: Hendrik Rathke; Clemens Kratochwil; Ralph Hohenberger; Frederik Lars Giesel; Frank Bruchertseifer; Paul Flechsig; Alfred Morgenstern; Matti Hein; Peter Plinkert; Uwe Haberkorn; Olcay Cem Bulut Journal: Eur J Nucl Med Mol Imaging Date: 2018-08-27 Impact factor: 9.236
Authors: Jorge A Carrasquillo; Bernard M Fine; Neeta Pandit-Taskar; Steven M Larson; Stephen E Fleming; Josef J Fox; Sarah M Cheal; Joseph A O'Donoghue; Shutian Ruan; Govind Ragupathi; Serge K Lyashchenko; John L Humm; Howard I Scher; Mithat Gönen; Simon P Williams; Daniel C Danila; Michael J Morris Journal: J Nucl Med Date: 2019-05-03 Impact factor: 10.057