Development of PDT/PET theranostics: synthesis and biological evaluation of an ¹⁸F-radiolabeled water soluble porphyrin

Entract, Guy M.; Bryden, Francesca; Domarkas, Juozas; Savoie, Huguette; Allott, Louis; Archibald, Stephen J.; Cawthorne, Chris; Boyle, Ross W.

Abstract

Synthesis of the first water-soluble porphyrin radiolabeled with fluorine-18 is described: a new molecular theranostic agent which integrates the therapeutic selectivity of photodynamic therapy (PDT) with the imaging efficacy of positron emission tomography (PET). Generation of the theranostic was carried out through the conjugation of a cationic water-soluble porphyrin bearing an azide functionality to a fluorine-18 radiolabeled prosthetic bearing an alkyne functionality through click conjugation, with excellent yields obtained in both cold and hot synthesis. Biological evaluation of the synthesized structures shows the first example of an 18 F-radiolabeled porphyrin retaining photocytotoxicity following radiolabeling and demonstrable conjugate uptake and potential application as a radiotracer in vivo. The promising results gained from biological evaluation demonstrate the potential of this structure as a clinically relevant theranostic agent, offering exciting possibilities for the simultaneous imaging and photodynamic treatment of tumors.

Citation

Entract, G. M., Bryden, F., Domarkas, J., Savoie, H., Allott, L., Archibald, S. J., Cawthorne, C., & Boyle, R. W. (2015). Development of PDT/PET theranostics: synthesis and biological evaluation of an ¹⁸F-radiolabeled water soluble porphyrin. Molecular pharmaceutics, 12(12), 4414-4423. https://doi.org/10.1021/acs.molpharmaceut.5b00606

• Journal Article Type: Article
• Acceptance Date: Nov 11, 2015
• Online Publication Date: Nov 11, 2015
• Publication Date: Dec 7, 2015
• Deposit Date: Dec 17, 2015
• Publicly Available Date: Dec 17, 2015
• Journal: Molecular pharmaceutics
• Print ISSN: 1543-8384
• Publisher: American Chemical Society
• Peer Reviewed: Peer Reviewed
• Volume: 12
• Issue: 12
• Pages: 4414-4423
• DOI: https://doi.org/10.1021/acs.molpharmaceut.5b00606
• Keywords: Flourine-18, PET imaging, Photodynamic therapy, Porphyrins, Theranostics
• Public URL: https://hull-repository.worktribe.com/output/382933
• Publisher URL: http://pubs.acs.org/doi/abs/10.1021/acs.molpharmaceut.5b00606
• Additional Information: This document is the Accepted Manuscript version of a Published Work that appeared in final form in Molecular pharmaceutics, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://dx.doi.org/10.1021/acs.molpharmaceut.5b00606
• Contract Date: Dec 17, 2015