Photoradiosynthesis of 68 Ga-Labeled HBED-CC-Azepin-MetMAb for Immuno-PET of c-MET Receptors

In an alternative approach for radiotracer design, a photoactivatable HBED-CC-PEG -ArN chelate was synthesized and photoconjugated to the anti-c-MET antibody MetMAb (onartuzumab). Photoconjugation gave the functionalized protein HBED-CC-azepin-MetMAb with a photochemical conversion of 18.5 ± 0.5% ( n = 2) which was then radiolabeled with Ga ions. The purified and formulated [ Ga]GaHBED-CC-azepin-MetMAb radiotracer was evaluated in vitro and in vivo. Standard stability tests and cellular binding assays confirmed that the radiotracer remained radiochemically pure and immunoreactive after photochemical conjugation. [ Ga]GaHBED-CC-azepin-MetMAb showed specific uptake in c-MET-positive MKN-45 (high-expression) and PC-3 (low/moderate expression) tumors with tumor-associated activities at 6 h post-administration of 10.33 ± 1.27 ( n = 5) and 3.88 ± 1.27 ( n = 3) %ID/g, respectively. In competitive blocking experiments, MKN-45 tumor uptake was reduced by approximately 55% ( P-value