Development of PDT/PET Theranostics: Synthesis and Biological Evaluation of an 18F-Radiolabeled Water-Soluble Porphyrin

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

doi:10.1021/acs.molpharmaceut.5b00606

Development of PDT/PET Theranostics: Synthesis and Biological Evaluation of an ¹⁸F-Radiolabeled Water-Soluble Porphyrin

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

^*Corresponding author for this work

Imaging Chemistry & Biology

Research output: Contribution to journal › Article › peer-review

27 Citations (Scopus)

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 ¹⁸F-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.

Original language	English
Pages (from-to)	4414-4423
Number of pages	10
Journal	Molecular Pharmaceutics
Volume	12
Issue number	12
DOIs	https://doi.org/10.1021/acs.molpharmaceut.5b00606
Publication status	Published - 11 Nov 2015

Keywords

fluorine-18
PET imaging
photodynamic therapy
porphyrins
theranostics

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title = "Development of PDT/PET Theranostics: Synthesis and Biological Evaluation of an 18F-Radiolabeled Water-Soluble Porphyrin",

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 18F-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.",

keywords = "fluorine-18, PET imaging, photodynamic therapy, porphyrins, theranostics",

author = "Entract, {Guy M.} and Francesca Bryden and Juozas Domarkas and Huguette Savoie and Louis Allott and Archibald, {Stephen J.} and Chris Cawthorne and Boyle, {Ross W.}",

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year = "2015",

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doi = "10.1021/acs.molpharmaceut.5b00606",

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AU - Entract, Guy M.

AU - Bryden, Francesca

AU - Domarkas, Juozas

AU - Savoie, Huguette

AU - Allott, Louis

AU - Archibald, Stephen J.

AU - Cawthorne, Chris

AU - Boyle, Ross W.

PY - 2015/11/11

Y1 - 2015/11/11

N2 - 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 18F-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.

AB - 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 18F-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.

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Development of PDT/PET Theranostics: Synthesis and Biological Evaluation of an ¹⁸F-Radiolabeled Water-Soluble Porphyrin

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