PET/PDT theranostics: synthesis and biological evaluation of a peptide-targeted gallium porphyrin

Abstract

The development of novel theranostic agents is an important step in the pathway towards personalised medicine, with the combination of diagnostic and therapeutic modalities into a single treatment agent naturally lending itself to the optimisation and personalisation of treatment. In pursuit of the goal of a molecular theranostic suitable for use as a PET radiotracer and a photosensitiser for PDT, a novel radiolabelled peptide–porphyrin conjugate targeting the α₆β₁-integrin has been developed. ^69/71Ga and ⁶⁸Ga labelling of an azide-functionalised porphyrin has been carried out in excellent yields, with subsequent bioconjugation to an alkyne-functionalised peptide demonstrated. α₆β₁-integrin expression of two cell lines has been evaluated by flow cytometry, and therapeutic potential of the conjugate demonstrated. Evaluation of the phototoxicity of the porphyrin–peptide theranostic conjugate in comparison to an untargeted control porphyrin in vitro, demonstrated significantly enhanced activity for a cell line with higher α₆β₁-integrin expression when compared with a cell line exhibiting lower α₆β₁-integrin expression.