Cherenkov Radiation induced photodynamic therapy - repurposing older photosensitizers, and radionuclides.

Autor: Lioret V; ICMUB Institute (Chemistry Department) Sciences Mirande, Université de Bourgogne Franche Comté, 9 Avenue Alain Savary, Dijon 21078, France., Bellaye PS; Centre George François Leclerc, 1 rue du Professeur Marion, Dijon 21079, France., Bernhard Y; ICMUB Institute (Chemistry Department) Sciences Mirande, Université de Bourgogne Franche Comté, 9 Avenue Alain Savary, Dijon 21078, France., Moreau M; ICMUB Institute (Chemistry Department) Sciences Mirande, Université de Bourgogne Franche Comté, 9 Avenue Alain Savary, Dijon 21078, France., Guillemin M; Centre George François Leclerc, 1 rue du Professeur Marion, Dijon 21079, France., Drouet C; Centre George François Leclerc, 1 rue du Professeur Marion, Dijon 21079, France., Collin B; ICMUB Institute (Chemistry Department) Sciences Mirande, Université de Bourgogne Franche Comté, 9 Avenue Alain Savary, Dijon 21078, France; Centre George François Leclerc, 1 rue du Professeur Marion, Dijon 21079, France., Decréau RA; ICMUB Institute (Chemistry Department) Sciences Mirande, Université de Bourgogne Franche Comté, 9 Avenue Alain Savary, Dijon 21078, France. Electronic address: richard.decreau@u-bourgogne.fr.
Jazyk: angličtina
Zdroj: Photodiagnosis and photodynamic therapy [Photodiagnosis Photodyn Ther] 2023 Dec; Vol. 44, pp. 103816. Date of Electronic Publication: 2023 Sep 30.
DOI: 10.1016/j.pdpdt.2023.103816
Abstrakt: Context: Old-generation photosensitizers are minimally used in current photodynamic therapy (PDT) because they absorb in the UV/blue/green region of the spectrum where biological tissues are generally highly absorbing. The UV/blue light of Cherenkov Radiation (CR) from nuclear disintegration of beta-emitter radionuclides shows promise as an internal light source to activate these photosensitizers within tissue. Outline of the study: 1) radionuclide choice and Cherenkov Radiation, 2) Photosensitizer choice, synthesis and radiolabeling, 3) CR-induced fluorescence, 4) Verification of ROS formation, 5) CR-induced PDT with either free eosine and free CR emitter, or with radiolabelled eosin.
Results: Cherenkov Radiation Energy Transfer (CRET) from therapeutic radionuclides ( 90 Y) and PET imaging radionuclides ( 18 F, 68 Ga) to eosin was shown by spectrofluorimetry and in vitro, and was shown to result in a PDT process. The feasibility of CR-induced PDT (CR-PDT) was demonstrated in vitro on B16F10 murine melanoma cells mixing free eosin (λ abs  = 524 nm, Φ Δ 0.67) with free CR-emitter [ 18 F]-FDG under their respective intrinsic toxicity levels (0.5 mM/8 MBq) and by trapping singlet oxygen with diphenylisobenzofuran (DPBF). An eosin-DOTAGA-chelate conjugate 1 was synthesized and radiometallated with CR-emitter [ 68 Ga] allowed to reach 25 % cell toxicity at 0.125 mM/2 MBq, i.e. below the toxicity threshold of each component measured on controls. Incubation time was carefully examined, especially for CR emitters, in light of its toxicity, and its CR-emitting yield expected to be 3 times as much for 68 Ga than 18 F (considering their β particle energy) per radionuclide decay, while its half-life is about twice as small.
Perspective: This study showed that in complete darkness, as it is at depth in tissues, PDT could proceed relying on CR emission from radionuclides only. Interestingly, this study also repurposed PET imaging radionuclides, such as 68 Ga, to trigger a therapeutic event (PDT), albeit in a modest extent. Moreover, although it remains modest, such a PDT approach may be used to achieve additional tumoricidal effect to RIT treatment, where radionuclides, such as 90 Y, are strong CR emitters, i.e. very potent light source for photosensitizer activation.
(Copyright © 2023 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: