Publikationsrepositorium - Helmholtz-Zentrum Dresden-Rossendorf

Ziel/Aim:

The bifunctional chelating agent 2-[4,7-bis(2-pyridylmethyl)-1,4,7-triazacyclononan-1-yl]acetic acid (DMPTACN-COOH) has been coupled to the stabilized bombesin (BBN) derivative [Cha13,Nle14]-BBN(7–14) using the spacer homo-Glu-Ala-Ala, was radiolabeled with the positron emitter copper-64, and the new radiotracer was preclinically characterized.

Methodik/Methods:

The in vitro and in vivo binding characteristics of the Cu-64-labeled bombesin conjugate in gastrin-releasing peptide receptor (GRPR) over-expressing prostate cancer (PC-3) cells/tumors have been evaluated. Biodistribution and metabolism studies were performed in Wistar rats. Small animal PET imaging was carried out to evaluate the biokinetics and tumor accumulation in tumor bearing NMRI nu/nu mice.

Ergebnisse/Results:

The pendant carboxylic group enables this derivative to be conjugated to the N-terminal amino acid residues of the peptide. The resulting radiocopper(II)-ligand complex exhibits high stability. The IC50 value on PC3 cells was 15 nM, the specific binding was confirmed by high uptake in the GRPR-rich pancreas used as reference organ. The peptide showed a good metabolic stability, however, it was fast eliminated by the kidneys. The PC3 tumors in the mice could be clearly imaged with tumor-to-muscle ratios steadily increasing over the time up to 30. The tumor uptake could be blocked by GRP.

Schlussfolgerungen/Conclusions:

Preclinical characterization of the Cu-64-labeled DMPTACN-COOH with incorporation of a single glutamic acid residue within the spacer between bombesin and the radiolabeled complex showed that the probe represents a promising GRPR radiotracer.