Effect of Cerenkov Radiation-Induced Photodynamic Therapy with 18F-FDG in an Intraperitoneal Xenograft Mouse Model of Ovarian Cancer.

Yi-An Chen,Sain-Jhih Chiu,Fong-Shya Jeng,Chi-Wei Chang,Cheng-Hsiu Lu,Chien-Chih Ke,Ren-Shyan Liu,Jia-Je Li,Bang-Hung Yang,Syue-Liang Lin,Ming-Cheng Chang

doi:10.3390/ijms22094934

Abstract

Ovarian cancer (OC) metastases frequently occur through peritoneal dissemination, and they contribute to difficulties in treatment. While photodynamic therapy (PDT) has the potential to treat OC, its use is often limited by tissue penetration depth and tumor selectivity. Herein, we combined Cerenkov radiation (CR) emitted by 18F-FDG accumulated in tumors as an internal light source and several photosensitizer (PS) candidates with matched absorption bands, including Verteporfin (VP), Chlorin e6 (Ce6) and 5′-Aminolevulinic acid (5′-ALA), to evaluate the anti-tumor efficacy. The in vitro effect of CR-induced PDT (CR-PDT) was evaluated using a cell viability assay, and the efficiency of PS was assessed by measuring the singlet oxygen production. An intraperitoneal ES2 OC mouse model was used for in vivo evaluation of CR-PDT. Positron emission tomography (PET) imaging and bioluminescence-based imaging were performed to monitor the biologic uptake of 18F-FDG and the therapeutic effect. The in vitro studies demonstrated Ce6 and VP to be more effective PSs for CR-PDT. Moreover, VP was more efficient in the generation of singlet oxygen and continued for a long time when exposed to fluoro-18 (18F). Combining CR emitted by 18F-FDG and VP treatment not only significantly suppressed tumor growth, but also prolonged median survival times compared to either monotherapy.

Highlights

Photodynamic therapy (PDT) is a minimally invasive form of therapy that has been clinically approved for treating non-oncological diseases as well as various types of cancers at the early stage [1,2]
The reduction of cell viability was found in a dose-dependent manner and remained ~80% of the control group when ES2 cells incubated with 3.7 MBq of 18F-FDG
We evaluated the effect of Cerenkov radiation (CR)-photodynamic therapy (PDT) on ES2 cells by combining 18F-FDG with the well-known PSs, 5 -Aminolevulinic acid (5 -ALA), methylene

Summary

Introduction

Photodynamic therapy (PDT) is a minimally invasive form of therapy that has been clinically approved for treating non-oncological diseases as well as various types of cancers at the early stage [1,2]. Light activates photosensitizers (PSs) to transform from the ground state to an excited state, producing reactive oxygen species (ROS) that cause cell damage. Since the light source utilized in clinical practices is external and commonly belongs to the visible light wavelength (400 to 800 nm), it exhibits limited tissue penetration (only up to 12 mm) within the body; it is not always effective when PDT is employed to deep-seated targets [3]. CR emitted from various medically relevant radioisotopes, such as 18F, 11C, 68Ga, 64Cu, 15O, 131I, etc., has been used in preclinical animal optical imaging equipment for Cerenkov luminescence imaging (CLI), and served as an endogenous light source for PDT [6,7]. Recent studies have confirmed its feasibility; the efficiency of combining PSs needs to be further evaluated

Objectives

Methods

Results

Discussion

Conclusion