The development of theranostic Positron Emission Tomography (PET)/Photodynamic Therapy (PDT) agents combines two promising areas of cancer research, providing both diagnostic and therapeutic action in a single compound. Incorporation of a PET-appropriate radioisotope allows quantitative evaluation of tumours, while PDT agents can subsequently treat the cancer with minimal damage to healthy tissue. Porphyrins represent excellent synthetic targets for these theranostics; they can be modified to be conjugatable and water-soluble, and the central cavity can act as a metal chelator, allowing radiolabelling without modification of the porphyrin skeleton. Ga-68 is of particular interest as it offers on-demand isotope production at low cost, while allowing retention of the photophysical properties of the porphyrin following complexation.Conjugation of porphyrins to tumour-targeting biomolecules allows improved uptake into target tissue, with peptides representing ideal targeting moieties due to their ease of modification, binding selectivity and rapid clearance from the body. The TWYKIAFQRNRK dodecapeptide was selected for use in this work as it specifically binds to the a6�1-intergrin, which is upregulated in glioblastoma cells and other cancers. While imaging applications for this peptide are limited due to activation of the intergrin and subsequent increased tumour invasiveness, it is a promising targeting agent for theranostics which allow treatment following imaging.In this work, the first example of both cold and hot gallium-complexation in a water-soluble, conjugatable porphyrin is demonstrated, with complexation carried out under aqueous conditions with minimal purification required. Optimisation of hot gallium insertion was carried out, with >95 % radiochemical yields obtained. Targeting with the FITC labelled dodecapeptide was demonstrated in vitro, and a �click� bioconjugation methodology between the porphyrin and peptide was optimised. Photobiological evaluation of the conjugate was carried out, with future work aiming to assess its suitability as a PET agent in appropriate in vitro and in vivo models.

PET/PDT theranostics: Synthesis and biological evaluation of a peptide-targeted Ga-68 porphyrin

248th National Meeting (2014)

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