OBJECTIVES: The present study describes the design and development of a series of new bombesin (BBN) antagonist peptide ligands of the form [(64)Cu-(NO2A-X-D-Phe(6)-BBN(6-13)NHEt)], where Cu-64=a positron emitting radiometal; NO2A=1,4,7-triazacyclononane-1,4-diacetic acid; X=6-amino hexanoic acid, 8-amino octanoic acid or 9-Aminononanoic acid; and BBN(6-13)NHEt=Gln-Trp-Ala-Val-Gly-His-Leu-NHEt, an antagonist analogue of bombesin peptide for specific targeting of the gastrin-releasing peptide receptor (GRPR). METHODS: [NO2A-X-D-Phe(6)-BBN(6-13)NHEt] conjugates were manually conjugated with NOTA (1,4,7-triazacyclononane-1,4,7-triacetic acid), and the resulting conjugates were labeled with (64)Cu to yield [(64)Cu-(NO2A-X-D-Phe(6)-BBN(6-13)NHEt)]. The metallated and nonmetallated conjugates were purified via reversed-phase high-performance liquid chromatography and characterized by electrospray ionization-mass spectrometry. RESULTS: Competitive displacement binding assays displayed nanomolar binding affinities toward human GRPR for all of the newly formed peptide analogues. Biodistribution studies showed very high uptake and retention of tumor-associated radioactivity in PC-3 (a prostate tumor model known to express the GRPR) tumor-bearing rodent models. The radiolabeled conjugates also exhibited rapid urinary excretion and very high tumor to background ratios. Micro-positron emission tomography (PET) molecular imaging investigations showed clear visualization of tumors in female PC-3 tumor-bearing mice 15 h postinjection. CONCLUSION: The biodistribution and molecular imaging study suggests that these conjugates can be considered as potential PET tracer candidates for the diagnosis of GRPR-positive tumors in human patients. Published by Elsevier Inc.
OBJECTIVES: The present study describes the design and development of a series of new bombesin (BBN) antagonist peptide ligands of the form [(64)Cu-(NO2A-X-D-Phe(6)-BBN(6-13)NHEt)], where Cu-64=a positron emitting radiometal; NO2A=1,4,7-triazacyclononane-1,4-diacetic acid; X=6-amino hexanoic acid, 8-amino octanoic acid or 9-Aminononanoic acid; and BBN(6-13)NHEt=Gln-Trp-Ala-Val-Gly-His-Leu-NHEt, an antagonist analogue of bombesin peptide for specific targeting of the gastrin-releasing peptide receptor (GRPR). METHODS: [NO2A-X-D-Phe(6)-BBN(6-13)NHEt] conjugates were manually conjugated with NOTA (1,4,7-triazacyclononane-1,4,7-triacetic acid), and the resulting conjugates were labeled with (64)Cu to yield [(64)Cu-(NO2A-X-D-Phe(6)-BBN(6-13)NHEt)]. The metallated and nonmetallated conjugates were purified via reversed-phase high-performance liquid chromatography and characterized by electrospray ionization-mass spectrometry. RESULTS: Competitive displacement binding assays displayed nanomolar binding affinities toward humanGRPR for all of the newly formed peptide analogues. Biodistribution studies showed very high uptake and retention of tumor-associated radioactivity in PC-3 (a prostate tumor model known to express the GRPR) tumor-bearing rodent models. The radiolabeled conjugates also exhibited rapid urinary excretion and very high tumor to background ratios. Micro-positron emission tomography (PET) molecular imaging investigations showed clear visualization of tumors in female PC-3 tumor-bearing mice 15 h postinjection. CONCLUSION: The biodistribution and molecular imaging study suggests that these conjugates can be considered as potential PET tracer candidates for the diagnosis of GRPR-positive tumors in humanpatients. Published by Elsevier Inc.
Authors: Sarah Marie Schwarzenböck; Philipp Schmeja; Jens Kurth; Michael Souvatzoglou; Roman Nawroth; Uwe Treiber; Guenther Kundt; Sandra Berndt; Keith Graham; Reingard Senekowitsch-Schmidtke; Markus Schwaiger; Sibylle I Ziegler; Ludger Dinkelborg; Hans-Jürgen Wester; Bernd Joachim Krause Journal: Mol Imaging Biol Date: 2016-06 Impact factor: 3.488
Authors: Rajendra Prasad Bandari; Zongrun Jiang; Tamila Stott Reynolds; Nicole E Bernskoetter; Ashley F Szczodroski; Kurt J Bassuner; Daniel L Kirkpatrick; Tammy L Rold; Gary L Sieckman; Timothy J Hoffman; James P Connors; Charles J Smith Journal: Nucl Med Biol Date: 2014-01-10 Impact factor: 2.408
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: Ying Li; Zhibo Liu; Curtis W Harwig; Maral Pourghiasian; Joseph Lau; Kuo-Shyan Lin; Paul Schaffer; Francois Benard; David M Perrin Journal: Am J Nucl Med Mol Imaging Date: 2013-01-05