title: Transforming a Targeted Porphyrin Theranostic Agent into a PET Imaging Probe for Cancer.
abstract: Porphyrin based photosensitizers are useful agents for photodynamic therapy (PDT) and fluorescence imaging of cancer. Porphyrins are also excellent metal chelators forming highly stable metallo-complexes making them efficient delivery vehicles for radioisotopes. Here we investigated the possibility of incorporating (64)Cu into a porphyrin-peptide-folate (PPF) probe developed previously as folate receptor (FR) targeted fluorescent/PDT agent, and evaluated the potential of turning the resulting (64)Cu-PPF into a positron emission tomography (PET) probe for cancer imaging. Noninvasive PET imaging followed by radioassay evaluated the tumor accumulation, pharmacokinetics and biodistribution of (64)Cu-PPF. (64)Cu-PPF uptake in FR-positive tumors was visible on small-animal PET images with high tumor-to-muscle ratio (8.88 ± 3.60) observed after 24 h. Competitive blocking studies confirmed the FR-mediated tracer uptake by the tumor. The ease of efficient (64)Cu-radiolabeling of PPF while retaining its favorable biodistribution, pharmacokinetics and selective tumor uptake, provides a robust strategy to transform tumor-targeted porphyrin-based photosensitizers into PET imaging probes.
authors.affiliation: 1. Department of Medical Biophysics, University of Toronto, Toronto, Canada;
authors.forename: Jiyun
authors.initials: J
authors.lastname: Shi
authors.forename: Tracy W B
authors.initials: TW
authors.lastname: Liu
authors.forename: Juan
authors.initials: J
authors.lastname: Chen
authors.forename: David
authors.initials: D
authors.lastname: Green
authors.forename: David
authors.initials: D
authors.lastname: Jaffray
authors.forename: Brian C
authors.initials: BC
authors.lastname: Wilson
authors.forename: Fan
authors.initials: F
authors.lastname: Wang
authors.forename: Gang
authors.initials: G
authors.lastname: Zheng