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Photoradiosynthesis of 68Ga-labelled HBED-CC-azepin-MetMAb for immuno-PET of c-MET receptors.
Bioconjugate Chemistry 2019 May 23
In an alternative approach for radiotracer design, a photoactivatable HBED-CC-PEG3-ArN3 chelate was synthesised and photoconjugated to the anti-c-MET antibody MetMAb (onartuzumab). Photoconjugation gave the functionalised protein HBED-CC-azepin-MetMAb with a photochemical conversion of 18.5±0.5% (n = 2) which was then radiolabelled with 68Ga3+ ions. The purified and formulated [68Ga]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. [68Ga]GaHBED-CC-azepin-MetMAb showed specific uptake in c-MET-positive MKN-45 (high-expression) and PC-3 (moderate expression) tumours with tumour-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 the competitive blocking experiments, MKN-45 tumour uptake was reduced by approximately 55% (P-value < 0.001 compared with non-blocked experiments) confirming specific radiotracer binding to c-MET in vivo. Radiochemical, cellular and in vivo experiments confirmed that this photoradiochemical approach is a viable tool to synthesise new radiotracers for immuno-PET.
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