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

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

doi:10.3390/ijms22094934

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

Int J Mol Sci. 2021 May 6;22(9):4934. doi: 10.3390/ijms22094934.

Authors

Yi-An Chen^{1

2}, Jia-Je Li³, Syue-Liang Lin^{3

4

5}, Cheng-Hsiu Lu^{2

6}, Sain-Jhih Chiu², Fong-Shya Jeng², Chi-Wei Chang⁷, Bang-Hung Yang^{3

7}, Ming-Cheng Chang⁸, Chien-Chih Ke^{9

10

11}, Ren-Shyan Liu^{1

2

3

6

12}

Affiliations

¹ Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan.
² Molecular and Genetic Imaging Core/Taiwan Mouse Clinic, National Comprehensive Mouse Phenotyping and Drug Testing Center, Taipei 112, Taiwan.
³ Department of Biomedical Imaging and Radiological Sciences, National Yang Ming Chiao Tung University, Taipei 112, Taiwan.
⁴ Department of Biotechnology and Laboratory Science in Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan.
⁵ Biomedical Engineering Research and Development Center Industrial, National Yang Ming Chiao Tung University, Taipei 112, Taiwan.
⁶ Industrial Ph.D Program of Biomedical Science and Engineering, National Yang Ming Chiao Tung University, Taipei 112, Taiwan.
⁷ National PET and Cyclotron Center (NPCC), Department of Nuclear Medicine, Taipei Veterans General Hospital, Taipei 112, Taiwan.
⁸ Institute of Nuclear Energy Research, Atomic Energy Council, Executive Yuan, Taoyuan County 325, Taiwan.
⁹ Department of Medical Imaging and Radiological Sciences, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
¹⁰ Drug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
¹¹ Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan.
¹² Department of Nuclear Medicine, Cheng Hsin General Hospital, Taipei 112, Taiwan.

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.

Keywords: 18F-FDG; Cerenkov radiation; ovarian cancer; photodynamic therapy; photosensitizer.

MeSH terms

Animals
Cell Line, Tumor
Female
Fluorodeoxyglucose F18 / therapeutic use*
Injections, Intraperitoneal
Mice
Mice, Inbred BALB C
Ovarian Neoplasms / therapy*
Photochemotherapy*
Radiation*
Xenograft Model Antitumor Assays*

Substances

Fluorodeoxyglucose F18

Grants and funding

MOST-109-2623-E-010-001-NU/Ministry of Science and Technology, Taiwan