Cancers
Pharmacokinetic-Modifying Linker Design Modulates Performance of Multivalent PSMA/GRPR-Cell-Targeting 177Lu Radiopharmaceuticals
By Claudia Chambers, Grace Liles, Anupam Mathur and 15 others.
Abstract
Background/Objectives: A series of PSMA/GRPR-targeting compounds were selected based on modifications to their respective pharmacokinetic-modifying linking groups and the structure of the PSMA-binding moiety, to examine how these alterations impact binding affinity and specificity for preclinical prostate cancer models.
Methods
The multi-receptor targeting heterodimers PSMA/2PSMA-X-DOTA-Y-BBN (where X is 6-aminohexanoic acid (6AHX) or polyethylene glycol-4 (PEG4) and Y is either 8-aminooctanoic acid (8AOC) or carboxy piperidine (CP)) were radiolabeled with the theranostic isotope [177Lu]Lu. Each heterodimer construct was evaluated through characterization, stability, whole-cell in vitro studies, biodistribution in tumor-bearing mice, and in vivo small animal SPECT/CT molecular imaging.