Added Value of Scintillating Element in Cerenkov-Induced Photodynamic Therapy

Abstract

Cerenkov-induced photodynamic therapy (CR-PDT) with the use of Gallium-68 (68Ga) as an unsealed radioactive source has been proposed as an alternative strategy to X-ray-induced photodynamic therapy (X-PDT). This new strategy still aims to produce a photodynamic effect with the use of nanoparticles, namely, AGuIX. Recently, we replaced Gd from the AGuIX@ platform with Terbium (Tb) as a nanoscintillator and added 5-(4-carboxyphenyl succinimide ester)-10,15,20-triphenylporphyrin (P1) as a photosensitizer (referred to as AGuIX@Tb-P1). Although Cerenkov luminescence from 68Ga positrons is involved in nanoscintillator and photosensitizer activation, the cytotoxic effect obtained by PDT remains controversial. Herein, we tested whether free 68Ga could substitute X-rays of X-PDT to obtain a cytotoxic phototherapeutic effect. Results were compared with those obtained with AGuIX@Gd-P1 nanoparticles. We showed, by Monte Carlo simulations, the contribution of Tb scintillation in P1 activation by an energy transfer between Tb and P1 after Cerenkov radiation, compared to the Gd-based nanoparticles. We confirmed the involvement of the type II PDT reaction during 68Ga-mediated Cerenkov luminescence, id est, the transfer of photon to AGuIX@Tb-P1 which, in turn, generated P1-mediated singlet oxygen. The effect of 68Ga on cell survival was studied by clonogenic assays using human glioblastoma U-251 MG cells. Exposure of pre-treated cells with AGuIX@Tb-P1 to 68Ga resulted in the decrease in cell clone formation, unlike AGuIX@Gd-P1. We conclude that CR-PDT could be an alternative of X-PDT.

Investigation of Photodynamic Therapy Promoted by Cherenkov Light Activated Photosensitizers—New Aspects and Revelations

“…Although our results differ from those of Yoon et al, there are other studies claiming significant effects of CL using Yttrium-90 (high energy beta-emitter similar to Re-188 with an even higher photon yield), Fluorine-18 or other standard radionuclides [ 55 , 57 , 58 , 59 , 60 ].…”

Non-targeted effects of radiation therapy for glioblastoma

“…Additionally, proton RT might offer the most practical means for delivering high-dose FLASH-RT (40 Gy s −1 versus 0.5–5 Gy min −1 for conventional RT) [ 46 ]. Moreover, recent advancements in nuclear medicine have also been suggested [ 47 ]. Nuclear medicine practitioners classically use β-particle emitters and in the field of GBM, these radionuclide can be linked to nanoparticles, monoclonal antibodies and/or peptides to induce a targeted approach, which is called selective internal radiation therapy.…”