Abstract
Gastrin-releasing peptide receptor (GRPR) is overexpressed by a variety of human tumors and in particular, identified to be upregulated in prostate cancers. The current study aimed to develop clinically translatable BBN analogue-based radioligands for positron emission tomography (PET) of GRPR-positive tumors. We developed radiolabeled BBN analogues and modified radiolabeled galacto-BBN analogues and then investigated their tumor-targeting efficacy in vivo. The chelator 1,4,7-triazacyclononane, 1-glutaric acid-4,7 acetic acid (NODAGA) was used to radiolabel the peptides with 64Cu. The peptides were evaluated by measuring cell-based receptor-binding affinities. Biodistribution experiments and small animal imaging using PET were performed in nude mice bearing subcutaneous PC3 human prostate cancer xenografts. The conjugates were radiolabeled with yields >99%. The stability assay showed that [64Cu]NODAGA-BBN and [64Cu]NODAGA-galacto-BBN remained stable in both human and mouse serum for 1 h at 37°C. PET images of PC3 tumor-bearing nude mice were acquired at 1, 3, 24, 48 and 72 h after injection. [64Cu]NODAGA-galacto-BBN showed retention in tumors for 72 h, low liver uptake, and rapid renal clearance. PET imaging results were also confirmed by biodistrubution 1 and 3 h after injection. [64Cu]NODAGA-BBN and [64Cu]NODAGA-galacto-BBN are promising new PET probes for GRPR-positive prostate cancer.
Original language | English |
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Pages (from-to) | 1159-1168 |
Number of pages | 10 |
Journal | International journal of oncology |
Volume | 46 |
Issue number | 3 |
DOIs | |
Publication status | Published - 2015 Mar 1 |
Keywords
- Bombesin
- Cu
- Positron emission tomography
- Prostate cancer
- Radiopharmaceuticals
ASJC Scopus subject areas
- Oncology
- Cancer Research