Selection of an optimal macrocyclic chelator improves the imaging of prostate cancer using cobalt-labeled GRPR antagonist RM26. Academic Article uri icon

Overview

abstract

  • Gastrin-releasing peptide receptors (GRPRs) are promising targets in oligometastatic prostate cancer. We have recently used 55Co (T1/2 = 17.5 h) as a label for next day PET imaging of GRPR expression obtaining high imaging contrast. The radionuclide-chelator combination can significantly influence the biodistribution of radiopeptides. Therefore, in this study, we hypothesized that the properties of 55Co-labeled PEG2-RM26 can be improved by identifying the optimal macrocyclic chelator. All analogues (X-PEG2-RM26, X = NOTA,NODAGA,DOTA,DOTAGA) were successfully labeled with radiocobalt with high yields and demonstrated high stability. The radiopeptides bound specifically and with picomolar affinity to GRPR and their cellular processing was characterized by low internalization. The best binding capacity was found for DOTA-PEG2-RM26. Ex vivo biodistribution in PC-3 xenografted mice was characterized by rapid blood clearance via renal excretion. Tumor uptake was similar for all conjugates at 3 h pi, exceeding the uptake in all other organs. Higher kidney uptake and longer retention were associated with N-terminal negative charge (DOTAGA-containing conjugate). Tumor-to-organ ratios increased over time for all constructs, although significant chelator-dependent differences were observed. Concordant with affinity measurements, DOTA-analog had the best retention of activity in tumors, resulting in the highest tumor-to-blood ratio 24 h pi, which translated into high contrast PET/CT imaging (using 55Co).

publication date

  • November 19, 2019

Research

keywords

  • Bombesin
  • Cobalt Radioisotopes
  • Macrocyclic Compounds
  • Organometallic Compounds
  • Positron-Emission Tomography
  • Prostatic Neoplasms
  • Receptors, Bombesin

Identity

PubMed Central ID

  • PMC6863848

Scopus Document Identifier

  • 85075208508

Digital Object Identifier (DOI)

  • 10.1016/j.bbrc.2013.10.149

PubMed ID

  • 31745219

Additional Document Info

volume

  • 9

issue

  • 1