PURPOSE: TF12 is a trivalent bispecific antibody that consists of two anti-TROP-2 Fab fragments and one anti-histamine-succinyl-glycine (HSG) Fab fragment. The TROP-2 antigen is found in many epithelial cancers, including prostate cancer (PC), and therefore this bispecific antibody could be suitable for pretargeting in this cancer. In this study, the characteristics and the potential for pretargeted radioimmunoimaging and radioimmunotherapy with TF12 and the radiolabeled di-HSG peptide IMP288 in mice with human PC were investigated. METHODS: The optimal TF12 protein dose, IMP288 peptide dose, and dose interval for PC targeting were assessed in nude mice with s.c. PC3 xenografts. Immuno-positron emission tomography (PET)/CT was performed using TF12/⁶⁸Ga-IMP288 at optimized conditions. The potential of pretargeted radioimmunotherapy (PRIT) using the TF12 pretargeted ¹⁷⁷Lu-IMP288 was determined. RESULTS: TF12 and ¹¹¹In-IMP288 showed high and fast accumulation in the tumor [20.4 ± 0.6%ID/g at 1 h post-injection (p.i.)] at optimized conditions, despite the internalizing properties of TF12. The potential for PRIT was shown by retention of 50% of the ¹¹¹In-IMP288 in the tumor at 48 h p.i. One cycle of treatment with TF12 and ¹⁷⁷Lu-IMP288 showed significant improvement of survival compared to treatment with ¹⁷⁷Lu-IMP288 alone (90 vs. 67 days, p<0.0001) with no renal or hematological toxicity. CONCLUSION: TROP-2-expressing PC can be pretargeted efficiently with TF12, with very rapid uptake of the radiolabeled hapten-peptide, IMP288, sensitive immuno-PET, and effective therapy.
PURPOSE:TF12 is a trivalent bispecific antibody that consists of two anti-TROP-2 Fab fragments and one anti-histamine-succinyl-glycine (HSG) Fab fragment. The TROP-2 antigen is found in many epithelial cancers, including prostate cancer (PC), and therefore this bispecific antibody could be suitable for pretargeting in this cancer. In this study, the characteristics and the potential for pretargeted radioimmunoimaging and radioimmunotherapy with TF12 and the radiolabeled di-HSG peptide IMP288 in mice with human PC were investigated. METHODS: The optimal TF12 protein dose, IMP288 peptide dose, and dose interval for PC targeting were assessed in nude mice with s.c. PC3 xenografts. Immuno-positron emission tomography (PET)/CT was performed using TF12/⁶⁸Ga-IMP288 at optimized conditions. The potential of pretargeted radioimmunotherapy (PRIT) using the TF12 pretargeted ¹⁷⁷Lu-IMP288 was determined. RESULTS:TF12 and ¹¹¹In-IMP288 showed high and fast accumulation in the tumor [20.4 ± 0.6%ID/g at 1 h post-injection (p.i.)] at optimized conditions, despite the internalizing properties of TF12. The potential for PRIT was shown by retention of 50% of the ¹¹¹In-IMP288 in the tumor at 48 h p.i. One cycle of treatment with TF12 and ¹⁷⁷Lu-IMP288 showed significant improvement of survival compared to treatment with ¹⁷⁷Lu-IMP288 alone (90 vs. 67 days, p<0.0001) with no renal or hematological toxicity. CONCLUSION:TROP-2-expressing PC can be pretargeted efficiently with TF12, with very rapid uptake of the radiolabeled hapten-peptide, IMP288, sensitive immuno-PET, and effective therapy.
Authors: Edmund A Rossi; David M Goldenberg; Thomas M Cardillo; William J McBride; Robert M Sharkey; Chien-Hsing Chang Journal: Proc Natl Acad Sci U S A Date: 2006-04-24 Impact factor: 11.205
Authors: William J McBride; Pat Zanzonico; Robert M Sharkey; Carl Norén; Habibe Karacay; Edmund A Rossi; Michele J Losman; Pierre-Yves Brard; Chien-Hsing Chang; Steven M Larson; David M Goldenberg Journal: J Nucl Med Date: 2006-10 Impact factor: 10.057
Authors: Rafke Schoffelen; Winette T A van der Graaf; Gerben Franssen; Robert M Sharkey; David M Goldenberg; William J McBride; Edmund A Rossi; Annemarie Eek; Wim J G Oyen; Otto C Boerman Journal: J Nucl Med Date: 2010-11 Impact factor: 10.057
Authors: Catharina M van Rij; Robert M Sharkey; David M Goldenberg; Cathelijne Frielink; Janneke D M Molkenboer; Gerben M Franssen; Wietske M van Weerden; Wim J G Oyen; Otto C Boerman Journal: J Nucl Med Date: 2011-08-24 Impact factor: 10.057
Authors: Robert M Sharkey; Catharina M van Rij; Habibe Karacay; Edmund A Rossi; Cathelijne Frielink; Celeste Regino; Thomas M Cardillo; William J McBride; Chien-Hsing Chang; Otto C Boerman; David M Goldenberg Journal: J Nucl Med Date: 2012-09-05 Impact factor: 10.057
Authors: Catharina M van Rij; Cathelijne Frielink; David M Goldenberg; Robert M Sharkey; Gerben M Franssen; Susanne Lütje; William J McBride; Wim J G Oyen; Otto C Boerman Journal: Mol Imaging Biol Date: 2015-02 Impact factor: 3.488
Authors: Catharina M van Rij; Cathelijne Frielink; David M Goldenberg; Robert M Sharkey; Susanne Lütje; William J McBride; Wim J G Oyen; Otto C Boerman Journal: Cancer Biother Radiopharm Date: 2014-09-16 Impact factor: 3.099
Authors: Françoise Kraeber-Bodéré; Caroline Rousseau; Caroline Bodet-Milin; Eric Frampas; Alain Faivre-Chauvet; Aurore Rauscher; Robert M Sharkey; David M Goldenberg; Jean-François Chatal; Jacques Barbet Journal: Front Pharmacol Date: 2015-03-31 Impact factor: 5.810