Novel Radiolabeled Peptides for Breast and Prostate Tumor PET Imaging: 64Cu/and 68Ga/NOTA-PEG-[d-Tyr6,尾Ala11,Thi13

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• 作者：Patrick Fournier ; V茅ronique Dumulon-Perreault ; Samia Ait-Mohand ; S茅bastien Tremblay ; Fran莽ois B茅nard ; Roger Lecomte ; Brigitte Gu茅rin
• 刊名：Bioconjugate Chemistry
• 出版年：2012
• 出版时间：August 15, 2012
• 年：2012
• 卷：23
• 期：8
• 页码：1687-1693
• 全文大小：286K
• 年卷期：v.23,no.8(August 15, 2012)
• ISSN：1520-4812

文摘

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, ⁶⁴Cu/and ⁶⁸Ga/NOTA-PEG-BBN(6鈥?4), 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; ⁶⁴Cu/NOTA-PEG-BBN(6鈥?4) was found to have the lowest inhibition constant (1.60 卤 0.59 nM). ⁶⁴Cu/and ⁶⁸Ga/NOTA-PEG-BBN(6鈥?4) 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 ⁶⁴Cu/NOTA-PEG-BBN(6鈥?4) presented higher GRPR-mediated uptake in pancreas and adrenal glands, but comparable PC3 tumor uptake as ⁶⁸Ga/NOTA-PEG-BBN(6鈥?4). 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 ⁶⁴Cu/NOTA-PEG-BBN(6鈥?4) and ⁶⁸Ga/NOTA-PEG-BBN(6鈥?4) are promising candidates for GRPR-targeted PET imaging of breast and prostate cancers.