Bombesin (BBN)-based radiolabeled
peptides exhibit promising properties for targeted imaging of
gastrin-releasing peptide receptors (GRPR)-positive
tumors. The aim of this study was to evaluate with positron emission tomography (PET) the pharmacokinetic and imaging properties of two novel BBN-based radiolabeled
peptides, (64)Cu/and (68)Ga/
NOTA-PEG-BBN(6-14), for diagnosis of breast and
prostate cancers using small animal models. Competitive binding assays on T47D breast and PC3
prostate cancer cells showed that the affinity for GRPR depends on the complexed
metal and can vary up to
a factor of about 3; (64)Cu/
NOTA-PEG-BBN(6-14) was found to have the lowest inhibition constant (1.60 ± 0.59 nM). (64)Cu/and (68)Ga/
NOTA-PEG-BBN(6-14) presented similar cell uptake on T47D and PC3 cells and were stable in vivo. Biodistribution studies of radiolabeled
peptides carried out in Balb/c and
tumor-bearing Balb/c nude mice showed that (64)Cu/
NOTA-PEG-BBN(6-14) presented higher GRPR-mediated uptake in pancreas and adrenal glands, but comparable PC3
tumor uptake as (68)Ga/
NOTA-PEG-BBN(6-14). Finally, receptor-dependent responses were observed during blocking studies with unlabeled
peptide in both biodistribution and small-animal PET imaging studies. Our results confirmed the dependence of the affinity and pharmacokinetics of BBN-based radiopeptides on the complexed radiometal. Interspecies differences between mouse and human GRPR binding properties were also noted in these preclinical studies. Considering their good imaging characteristics, both (64)Cu/
NOTA-PEG-BBN(6-14) and (68)Ga/
NOTA-PEG-BBN(6-14) are promising candidates for GRPR-targeted PET imaging of breast and
prostate cancers.