title: 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. (69/71)Ga and (68)Ga 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.
authors.affiliation: Department of Chemistry, University of Hull, Cottingham Road, HU6 7RX, UK. r.w.boyle@hull.ac.uk.
authors.forename: Francesca
authors.initials: F
authors.lastname: Bryden
authors.forename: Huguette
authors.initials: H
authors.lastname: Savoie
authors.forename: Elena V
authors.initials: EV
authors.lastname: Rosca
authors.forename: Ross W
authors.initials: RW
authors.lastname: Boyle
mesh_terms: D000480:Alkynes / Q000737:chemistry; D000595:Amino Acid Sequence; D001386:Azides / Q000737:chemistry; D002384:Catalysis; D003300:Copper / Q000737:chemistry; D061565:Cycloaddition Reaction; D005710:Gallium Radioisotopes / Q000627:therapeutic use; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D008665:Metalloporphyrins / Q000737:chemistry*; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*; D049268:Positron-Emission Tomography; D013696:Temperature
chemical_list: D000480:Alkynes; D001386:Azides; D005710:Gallium Radioisotopes; D008665:Metalloporphyrins; D010455:Peptides; D017319:Photosensitizing Agents; D003300:Copper