Abstract
1465
Objectives: Bombesin (BBN) binds with high affinity to the gastrin-releasing peptide receptor (GRPR). GRPR is overexpressed in many breast and prostate cancers. The objective of this study was to evaluate 64Cu-DOTA-8-Aoc-BBN(7-14)NH2, a BBN analog, as a potential tracer for breast and prostate cancer imaging. Methods: 64Cu-DOTA-8-Aoc-BBN(7-14)NH2 was tested in vitro by saturation radioligand and homologous competitive binding assays. Mouse breast (MC7-L1 and MC4-L2) and human breast and prostate cancer cells (PC-3, T47D and MCF-7) were incubated with increasing concentrations of the cold tracer to determine the presence of GRPR. In vivo experiment were performed with tumor MC7-L1 and MC4-L2 or PC-3 implanted on mice. The animals were sacrificed after 30, 60 or 120 min. A control was also carried out with co-injection of cold peptide. GRPR expression was also measured with 125I-BBN in the murine cell lines. Results: Minimal levels of GRPR were observed in the murine cell lines, using either DOTA-8-Aoc-BBN(7-14)NH2 or 125I-BBN, while good receptor expression was noted in MCF-7, T47D breast and PC-3 prostate cancer cells. The in vivo experiments were conducted by the injection of 10 to 300 mCi of 64Cu-BBN. The %i.d./g at 60min were 3.02±0.66, 3.31±1.48, 3.68±0.24, 3.20±0.39 and 2.67±0.32 for the MC7-L1, MC4-L2, PC-3, T47D and MCF-7 cell lines, respectively. The peak tumor-to-blood ratios were 2.59±0.82, 3.35±0.30, 3.24±1.57, 2.43±0.35 and 2.26±0.66 respectively. Uptake in the pancreas dropped by 90% with co-injection of the unlabelled peptide, while no significant change was observed in tumor uptake. Significant tumor uptake of CuCl2 and Cu-acetate was noted at 60min (4.32±0.11%i.d./g and 2.02±0.21%i.d./g). Conclusions: A high level of GRPR expression was noted in the human breast and prostate tumor cell lines. Murine breast cancer cell lines are unsuitable to assess GRPR expression in tumors, probably due to interspecies differences. Although 64Cu-DOTA-8-Aoc-BBN(7-14)NH2 depicts specific receptor mediated uptake in the pancreas, tumor uptake is confounded by a background of 64Cu uptake not mediated by GRPR expression.
Research Support (if any): Canadian Breast Cancer Research Alliance
- Society of Nuclear Medicine, Inc.