Background: Radionuclide molecular imaging of Gastrin-Releasing Peptide Receptor
(GRPR) expression promises unparalleled opportunities for visualizing subtle prostate tumors, which
due to small size, adjacent benign tissue, or a challenging location would otherwise remain undetected
by conventional imaging. Achieving high imaging contrast is essential for this purpose and the molecular
design of any probe for molecular imaging of prostate cancer should be aimed at obtaining as high
tumor-to-organ ratios as possible.
Objective: This short review summarizes the key imaging modalities currently used in prostate cancer,
with a special focus on radionuclide molecular imaging. Emphasis is laid mainly on the issue of radiometals
labeling chemistry and its influence on the targeting properties and biodistribution of radiolabeled
GRPR antagonists for imaging of disseminated prostate cancer.
Methods: A comprehensive literature search of the PubMed/MEDLINE, and Scopus library databases
was conducted to find relevant articles.
Results: The combination of radionuclide, chelator and required labeling chemistry was shown to have
a significant influence on the stability, binding affinity and internalization rate, off-target interaction
with normal tissues and blood proteins, interaction with enzymes, activity uptake and retention in excretory
organs and activity uptake in tumors of radiolabeled bombesin antagonistic analogues.
Conclusion: Labeling chemistry has a very strong impact on the biodistribution profile of GRPRtargeting
peptide based imaging probes and needs to be considered when designing a targeting probe
for high contrast molecular imaging. Taking into account the complexity of in vivo interactions, it is not
currently possible to accurately predict the optimal labeling approach. Therefore, a detailed in vivo
characterization and optimization is essential for the rational design of imaging agents.