TY - JOUR T1 - A Novel Radiotracer for Molecular Imaging and Therapy of Gastrin-Releasing Peptide Receptor Positive Prostate Cancer JF - Journal of Nuclear Medicine JO - J Nucl Med DO - 10.2967/jnumed.120.257758 SP - jnumed.120.257758 AU - Francois Benard AU - Ivica Jerolim Bratanovic Y1 - 2021/07/01 UR - http://jnm.snmjournals.org/content/early/2021/07/22/jnumed.120.257758.abstract N2 - The gastrin-releasing peptide receptor (GRPR) is overexpressed in many solid malignancies, particularly in prostate and breast cancers, among others. We synthesized ProBOMB2, a novel bombesin derivative radiolabeled with 68Ga and 177Lu, and evaluated its ability to target GRPR in a preclinical model of human prostate cancer. Methods: ProBOMB2 was synthesized on solid phase using Fmoc chemistry. The chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid was coupled to the N-terminus and separated from the GRPR-targeting sequence by a cationic 4-amino-(1-carboxymethyl)-piperidine spacer. Binding affinity for both human and murine GRPR was determined using a cell-based competition assay, while a calcium efflux assay was used to measure the agonist/antagonist properties of the derivatives. ProBOMB2 was radiolabeled with 177Lu and 68Ga. SPECT and PET imaging, and biodistribution studies were conducted using a preclinical prostate cancer model of male immunocompromised mice bearing GRPR-positive PC-3 human prostate cancer xenografts. Results: Ga-ProBOMB2 and Lu-ProBOMB2 bound to PC-3 cells with a Ki of 4.58±0.67 and 7.29±1.73 nM, respectively. 68Ga-ProBOMB2 and 177Lu-ProBOMB2 were radiolabeled with a radiochemical purity greater than 95%. Both radiotracers were primarily excreted via the renal pathway. PET images of PC-3 tumor xenografts were visualized with excellent contrast at 1 h and 2 h post-injection (p.i.) with 68Ga-ProBOMB2, and very low off-target organ accumulation. 177Lu-ProBOMB2 enabled clear visualization of PC-3 tumor xenografts by SPECT imaging at 1 h, 4 h, and 24 h p.i. 177Lu-ProBOMB2 displayed higher tumor uptake than 68Ga-ProBOMB2 at 1 h p.i. 177Lu-ProBOMB2 tumor uptake at 1 h, 4 h, and 24 h p.i. was 14.9±3.1, 4.8±2.1, and 1.7±0.3 %ID/g, respectively. Conclusion: 68Ga-ProBOMB2 and 177Lu-ProBOMB2 are promising radiotracers with limited pancreas uptake, good tumor uptake, and favorable pharmacokinetics for imaging and therapy of GRPR-expressing tumors. ER -