Synthesis and evaluation of Ga-68 labeled Y2-selective peptides for in vivo receptor targeting using small animal PET

Peptide YY (PYY) is a 36 amino acid peptide amide that belongs to the PP-hormone family. It selectively binds to at least two G-protein coupled receptors named Y2- and Y5-receptor. These receptors are overexpressed in various tumors like neuroblastomas and nephroblastomas. With regard to clinical applications, NPY2 and NPY5 receptors may act as in vivo targets for receptor-directed therapy and diagnosis of the tumors, however there are specific and in vivo stabile ligands still required. The aim of the work was to synthesize receptor ligands, which could be radioloabeled with the positron emitting nuclides Ga-68 for small animal positron emission tomography (PET).
PYY derivatives were synthesized by solid-phase peptide synthesis, characterized by HPLC/MALDI techniques, purified by preparative HPLC and linked to DOTA (1,4,7,10-tetraazacyclotetradecane-N, N´,N´´,N´´´tetraacetic acid) as chelator for the ⁶⁸Ga(III). The in vitro binding affinity of the peptides was studied in SMS-KAN cells expressing NPY2 receptors by competitive receptor binding assays. Two Ga-68 labeled derivatives were studied in vivo by small animal PET in rats and mice. The activity was fast eliminated into the urine. One hour after injection was only in the kidneys remaining activity detected.
Optimized Y2-selective and in vivo stabile peptides will be developed and tested for tumor targeting.