Publications Repository - Helmholtz-Zentrum Dresden-Rossendorf

2 Publications
Small animal PET with new Cu-64-chelating ligands coupled to stabilized bombesin
Bergmann, R.; Walther, M.; Juran, S.; Gasser, G.; Pietzsch, J.; Stephan, H.; Steinbach, J.;
Aim: Gastrin releasing peptide receptors (GRPR) are overexpressed in different human tumors like prostate, breast and squamous cell carcinomas. The goal of this study was to compare the biodistribution and metabolism of a stabilized bombesin analogue radiolabeled with two new Cu-64-complexes for PET imaging of GRPR expression in xenografted mice.

Methods: Cu-64 was complexed with a bis(2-pyridylmethyl) derivative of 1,4,7-triazacyclononane (TAC) and a bispidine 1,5-dicarboxylic acid derivative (Cu-64-N2Py4-OH(COOH)2) conjugated to a stabilized bombesin (BBN) derivative βhomoGlu-βAla-βAla-[Cha13, Nle14]BN(7-14) (Garcia Garoya et al. 2007). Biodistribution, elimination, and metabolism were studied in rats. Tumor accumulation was exemplarily evaluated with small animal PET in xenografted mice bearing prostate (PC3), squamous cell carcinoma (FaDu), and colorectal (HT-29) human tumors. Cu-64 chloride was studied for comparison.

Results: PET imaging of Cu-64-N2Py4-OH(COOH)2-BBN in mice 1 h after injection revealed tumor-to-background ratios of 2.1 (PC3), 2.4 (FaDu control), 1.0 (FaDu blocked), and 1.5 (HT-29). The uptake found in PC3 tumors with tissue sampling was significantly higher (5.3 control; 2.6 blocked). In comparison to the Cu-64-TAC-BBN, the uptake of Cu-64-N2Py4-OH(COOH)2-BBN in rat pancreas and intestine was lower but the accumulation in kidney, liver, and stomach was higher. The metabolic stabilities of the Cu-64-labeled BBN‘s studied were comparable. More than 85% of the original substances were remained after 1 hour in vitro incubation with rat blood or blood plasma. In vivo all compounds were fast metabolized in rats, and lower than 5% of the original compounds were recovered in arterial blood plasma 1 hour after injection. However, the metabolism in xenografted nude mice was slower, after 1 hour 12% of blood plasma activity correspond to the original compound.

Conclusion: Both investigated new Cu-64 chelating agents conjugated to a stabilized BBN analogue showed typical BBN biodistribution and GRPR specific accumulation in vivo. The differences in biodistribution and metabolism between Cu-64-TAC- and Cu-64-N2Py4-OH(COOH)2) labeled BBN demonstrate the influence of the Cu-64 chelating units on these processes, especially on the nonspecific activity biodistribution. Comparison of biodistribution data of the BBN analogues and Cu-64 chloride indicate only marginal, if any, in vivo copper demetalation, revealing high in vivo stability of the copper complex units. With further optimization of the radiolabeling in particular of specific activity the low specific uptake should increase. The studied chelating agents appear to be promising candidates for copper labeling of peptides under mild conditions.
Partly supported by the 6th framework EU-project “BioCare”, proposal # 505785.
  • Abstract in refereed journal
    Nuklearmedizin 48(2009)2, A56
  • Lecture (Conference)
    47. Jahrestagung der Deutschen Gesellschaft für Nuklearmedizin, 22.-25.04.2009, Leipzig, Deutschland

Publ.-Id: 11901 - Permalink