Use of 68Gallium for Cerenkov-induced Photodynamic effect on human U-251 MG glioblastoma cell line

• Published in: Photodiagnosis and photodynamic therapy 2023-03, Vol.41, p.103486, Article 103486
• Main Authors: SCHNELLER, Perrine, DAOUK, Joël, COLLET, Charlotte, BEEN, Quentin, DHAINI, Batoul, ARNOUX, Philippe, ROCCHI, Paul, LUX, François, TILLEMENT, Olivier, FROCHOT, Céline, BARBERI-HEYOB, Muriel, SCHOHN, Hervé
• Format: Article
• Language: English
• Subjects: Cerenkov-induced or X-ray-induced Photodynamic Therapy; glioblastoma; nanoparticle; porphyrin
• ISSN: 1572-1000; 1873-1597
• DOI: 10.1016/j.pdpdt.2023.103486

X-ray-induced Photodynamic Therapy (X-PDT) is an alternative strategy to improve Photo Dynamic Therapy (PDT) for cancer treatment [1]. The X-PDT principle is based on the conversion of X-ray photons into visible photons, from nanoscintillator embedded in nanoparticles (NPs) and linked to the photosensitizer, which, in turn, produces singlet oxygen and reactive species. Recently, several lines of evidence demonstrated that radionuclides can be used instead of X-rays irradiation to produce similar photodynamic effect, using NPs containing both nanoscintillator and photosensitizer. [1]. The obtained results are related to the Cerenkov luminescence and it is based on the positrons emission along lifetime of the radionuclides [2]. The ultra-small Gadolinium (Gd) based nanoparticle, namely AGuIX®, were initially designed for a non-toxic resonance magnetic agent and for its imaging properties [3]. Recently, we replaced Gd from the AGuIX@ platform by Terbium and added 5-(4-carboxyphenyl succinimide ester)-10,15,20-triphenylporphyrin (P1) [4]. The new NP, referred as AGuIX@Tb-P1, was characterized for its photo-physical and biological properties. We demonstrated that the NP design is compatible for X-PDT. Using U-251 MG human glioblastoma cells, we showed that AGuIX@Tb-P1 pre-treated cells exposed to X-rays underwent cell growth arrest with an enhanced factor of 35%, when the results were compared to those obtained with untreated cells exposed to X-rays [4]. Based on our results, we assessed whether free Gallium-68 (68Ga) could be used in order to substitute X-ray irradiation, using the same experimental procedure as previously described [4]. We showed i) that 68Ga-mediated Cerenkov luminescence is sufficient to transfer photon to AGuIX@Tb-P1 whose produced P1-mediated singlet oxygen under Cerenkov radiation; ii) U-251 MG cell exposure to 68Ga reduced cell clone formation. Both irradiation procedures were associated to change in the redox statue providing evidence of reactive derived oxygen species production. In conclusion, free 68Ga could be substituted to X-ray to produce a photodynamic effect, in our experimental conditions, using AGuIX@Tb-P1, in order to limit X- ray dose and radiation-mediated damage on tumor environment.