PURPOSE: In vivo imaging of α(v)β(3) has important diagnostic and therapeutic applications. (18)F-Galacto-arginine-glycine-aspartic acid (RGD) has been developed for positron emission tomography (PET) imaging of integrin α(v)β(3) expression and is now being tested on humans. Dimerization and multimerization of cyclic RGD peptides have been reported to improve the integrin α(v)β(3)-binding affinity due to the polyvalency effect. Here, we compared a number of new dimeric RGD peptide tracers with the clinically used (18)F-galacto-RGD. PROCEDURES: RGD monomers and dimers were coupled with galacto or PEG(3) linkers, and labeled with (18)F using 4-nitrophenyl 2-(18)F-fluoropropionate ((18)F-NFP) or N-succinimidyl 4-(18)F-fluorobenzoate as a prosthetic group. The newly developed tracers were evaluated by cell-based receptor-binding assay, biodistribution, and small-animal PET studies in a subcutaneous U87MG glioblastoma xenograft model. RESULTS: Starting with (18)F-F(-), the total reaction time for (18)F-FP-SRGD2 and (18)F-FP-PRGD2 is about 120 min. The decay-corrected radiochemical yields for (18)F-FP-SRGD2 and (18)F-FP-PRGD2 are 52 ± 9% and 80 ± 7% calculated from (18)F-NFP. Noninvasive small-animal PET and direct tissue sampling experiments demonstrated that the dimeric RGD peptides had significantly higher tumor uptake as compared to (18)F-galacto-RGD. CONCLUSION: Dimeric RGD peptide tracers with relatively high tumor integrin-specific accumulation and favorable in vivo kinetics may have the potential to be translated into clinic for integrin α(v)β(3) imaging.
PURPOSE: In vivo imaging of α(v)β(3) has important diagnostic and therapeutic applications. (18)F-Galacto-arginine-glycine-aspartic acid (RGD) has been developed for positron emission tomography (PET) imaging of integrin α(v)β(3) expression and is now being tested on humans. Dimerization and multimerization of cyclic RGD peptides have been reported to improve the integrin α(v)β(3)-binding affinity due to the polyvalency effect. Here, we compared a number of new dimeric RGD peptide tracers with the clinically used (18)F-galacto-RGD. PROCEDURES: RGD monomers and dimers were coupled with galacto or PEG(3) linkers, and labeled with (18)F using 4-nitrophenyl 2-(18)F-fluoropropionate ((18)F-NFP) or N-succinimidyl 4-(18)F-fluorobenzoate as a prosthetic group. The newly developed tracers were evaluated by cell-based receptor-binding assay, biodistribution, and small-animal PET studies in a subcutaneous U87MGglioblastoma xenograft model. RESULTS: Starting with (18)F-F(-), the total reaction time for (18)F-FP-SRGD2 and (18)F-FP-PRGD2 is about 120 min. The decay-corrected radiochemical yields for (18)F-FP-SRGD2 and (18)F-FP-PRGD2 are 52 ± 9% and 80 ± 7% calculated from (18)F-NFP. Noninvasive small-animal PET and direct tissue sampling experiments demonstrated that the dimeric RGD peptides had significantly higher tumor uptake as compared to (18)F-galacto-RGD. CONCLUSION: Dimeric RGD peptide tracers with relatively high tumor integrin-specific accumulation and favorable in vivo kinetics may have the potential to be translated into clinic for integrin α(v)β(3) imaging.
Authors: Ambros J Beer; Roland Haubner; Mario Sarbia; Michael Goebel; Stephan Luderschmidt; Anca Ligia Grosu; Oliver Schnell; Markus Niemeyer; Horst Kessler; Hans-Jürgen Wester; Wolfgang A Weber; Markus Schwaiger Journal: Clin Cancer Res Date: 2006-07-01 Impact factor: 12.531
Authors: Ambros J Beer; Roland Haubner; Ingo Wolf; Michael Goebel; Stephan Luderschmidt; Markus Niemeyer; Anca-Ligia Grosu; Maria-Jose Martinez; Hans Jürgen Wester; Wolfgang A Weber; Markus Schwaiger Journal: J Nucl Med Date: 2006-05 Impact factor: 10.057
Authors: Ingrid Dijkgraaf; John A W Kruijtzer; Shuang Liu; Annemieke C Soede; Wim J G Oyen; Frans H M Corstens; Rob M J Liskamp; Otto C Boerman Journal: Eur J Nucl Med Mol Imaging Date: 2006-08-15 Impact factor: 9.236
Authors: Xiaoyuan Chen; Shuang Liu; Yingping Hou; Michel Tohme; Ryan Park; James R Bading; Peter S Conti Journal: Mol Imaging Biol Date: 2004 Sep-Oct Impact factor: 3.488
Authors: Toshiro Kitagawa; Hisanori Kosuge; Edwin Chang; Michelle L James; Tomoaki Yamamoto; Bin Shen; Frederick T Chin; Sanjiv S Gambhir; Ronald L Dalman; Michael V McConnell Journal: Circ Cardiovasc Imaging Date: 2013-08-30 Impact factor: 7.792