Evaluation of a ⁶⁴Cu-labeled 1,4,7-triazacyclononane, 1-glutaric acid-4,7 acetic acid (NODAGA)-galactose-bombesin analogue as a PET imaging probe in a gastrin-releasing peptide receptor-expressing prostate cancer xenograft model

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.