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

Abstract

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 64 cu. 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

PET Probes for Preclinical Imaging of GRPR-Positive Prostate Cancer: Comparative Preclinical Study of [68Ga]Ga-NODAGA-AMBA and [44Sc]Sc-NODAGA-AMBA

“…In accordance with in-vivo and ex-vivo studies, significantly decreased tracer uptake of the GRPR-positive PC-3 cells was depicted in the case of the blocking experiments, whereas the blocking agent expressed no effect on control HaCaT cells. In line with our results, Kim et al reported discrete tumor uptake of [ 64 Cu]Cu-NODAGA-BBN or [ 64 Cu]Cu-NODAGA-galacto-BBN following the administration of 15 mg/BW of non-radioactive blocking ligands (NODAGA-BBN, or NODAGA-galacto-BBN) [ 37 ]. They presented the reduction of the radiopharmaceutical accumulation in the group of PC-3 tumor-bearing nude mice injected with the GRPR-blocking agent 30 min prior to the tracer administration compared to those pets that did not receive the blocking ligand [ 37 ].…”

Early Prediction of Radiation-Induced Pulmonary Fibrosis Using Gastrin-Releasing Peptide Receptor-Targeted PET Imaging

“…As a result, tumor uptake of [ 64 Cu]Cu-NODAGA-galacto-BBN decreased significantly in the group treated with the blocking agent (0.14 ± 0.05 %ID/g) compared with the group that did not receive the blocking agent (1.46 ± 1.20 %ID/g). 36 In this study, we acquired [ 64 Cu]Cu-NODAGA-galacto-BBN PET/CT images of mice with RIPF at 0, 2, 5, and 11 weeks after irradiating lungs with 90 Gy. When lung tissue is irradiated, inflammation is induced and mediates the progression of pulmonary fibrosis; therefore, we also acquired [ 18 F]F-FDG PET/CT images of mice with RIPF as markers for inflammation and the degree of fibrosis and compared them with GRPR-targeted imaging.…”

“…The synthesis of NODAGA-galacto-BBN(7–14)­NH 2 was conducted by FUTURECHEM (Seoul, Korea), as described in a previous study . Briefly, d -galacturonic acid was conjugated to the amine of glutamine on BBN(7–14)­NH 2 via an ester.…”

“…It has been previously reported that blocking the gastrin-releasing peptide receptor (GRPR) in irradiated lung tissue of mice suppresses inflammation by decreasing the number of macrophages and fibroblasts and further reducing the amount of collagen, , indicating that GRPR and GRP mediate the progression of RIPF and are possible targets for the early prediction of RIPF. Previously, our group successfully synthesized the PET imaging probe [ 64 Cu]­Cu-NODAGA-galacto-bombesin (BBN) using an analogue of GRP and demonstrated that [ 64 Cu]­Cu-NODAGA-galacto-BBN targets GRPR with high affinity . In this study, we evaluated whether [ 64 Cu]­Cu-NODAGA-galacto-BBN could predict early-stage RIPF by acquiring PET images at 0, 2, 5, and 11 weeks after irradiation of the lungs of mice and compared the expression of GRPR and GRP, inflammation, and fibrosis levels.…”

New Frontiers in Molecular Imaging Using Peptide-Based Radiopharmaceuticals for Prostate Cancer

“…Chelators serve not only to chelate and stabilize radionuclides but also to tether them to other molecules via a chemically active functional group without causing undesirable changes in biodistribution, target binding, and pharmacokinetic. Kim et al (2015) developed clinically translatable BBN analog-based radiopharmaceuticals for the PET imaging of GRPR-overexpressed tumors. In that study, the chelator 1,4,7-triazacyclononane, 1-glutaric acid-4,7 acetic acid (NODAGA) was used to radiolabel BBN analogs and modified galacto-BBN analogs with 64 Cu.…”