title: Novel radiolabeled peptides for breast and prostate tumor PET imaging: (64)Cu/and (68)Ga/NOTA-PEG-[D-Tyr(6),βAla(11),Thi(13),Nle(14)]BBN(6-14).
abstract: 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.
authors: Centre d'imagerie moléculaire de Sherbrooke (CIMS), Centre Hospitalier Universitaire de Sherbrooke, Université de Sherbrooke, 3001, 12th Avenue North, Sherbrooke, Quebec, Canada, J1H 5N4.
authors: Patrick
authors: P
authors: Fournier
authors: Véronique
authors: V
authors: Dumulon-Perreault
authors: Samia
authors: S
authors: Ait-Mohand
authors: Sébastien
authors: S
authors: Tremblay
authors: François
authors: F
authors: Bénard
authors: Roger
authors: R
authors: Lecomte
authors: Brigitte
authors: B
authors: Guérin
mesh_terms: D000818:Animals; D001839:Bombesin / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology; D003301:Copper Radioisotopes; D004355:Drug Stability; D005710:Gallium Radioisotopes; D006571:Heterocyclic Compounds / Q000737:chemistry*; D006573:Heterocyclic Compounds, 1-Ring; D006801:Humans; D007553:Isotope Labeling; D008297:Male; D051379:Mice; D011092:Polyethylene Glycols / Q000737:chemistry*; D049268:Positron-Emission Tomography / Q000379:methods*; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology; D021381:Protein Transport
chemical_list: D003301:Copper Radioisotopes; D005710:Gallium Radioisotopes; D006571:Heterocyclic Compounds; D006573:Heterocyclic Compounds, 1-Ring; D011092:Polyethylene Glycols; C048993:1,4,7-triazacyclononane-N,N',N''-triacetic acid; D001839:Bombesin