Basic Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Radiol. Nov 28, 2023; 15(11): 315-323
Published online Nov 28, 2023. doi: 10.4329/wjr.v15.i11.315
Imaging assessment of photosensitizer emission induced by radionuclide-derived Cherenkov radiation using charge-coupled device optical imaging and long-pass filters
Winn Aung, Atsushi B Tsuji, Kazuaki Rikiyama, Fumihiko Nishikido, Satoshi Obara, Tatsuya Higashi
Winn Aung, Atsushi B Tsuji, Kazuaki Rikiyama, Satoshi Obara, Tatsuya Higashi, Department of Molecular Imaging and Theranostics, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan
Fumihiko Nishikido, Department of Advanced Nuclear Medicine Sciences, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan
Author contributions: Aung W conceptualized and designed the study; Aung W, Rikiyama K and Nishikido F conducted the experiments and analyzed the data; Obara S performed the subtraction image processing; Aung W and Tsuji AB wrote the manuscript; Tsuji AB and Higashi T coordinated the research and contributed to manuscript preparation; all authors contributed to manuscript revision; All authors read and approved the final manuscript.
Supported by Grant-in-Aid for Scientific Research (C) from the Japan Society for the Promotion of Science, No. 21K07740.
Institutional review board statement: This study was reviewed and approved by the Institutional Review Board of National Institutes for Quantum Science and Technology, No. 07-1064-28. No animals or animal-derived samples or patients or patient-derived samples were included in this study.
Conflict-of-interest statement: The authors declare no potential conflicts of interest for this article.
Data sharing statement: All relevant data were presented in the manuscript. Further information is available from the corresponding author at winn.aung@qst.go.jp.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Winn Aung, MBBS, PhD, Senior Researcher, Department of Molecular Imaging and Theranostics, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan. winn.aung@qst.go.jp
Received: October 3, 2023
Peer-review started: October 3, 2023
First decision: October 17, 2023
Revised: October 26, 2023
Accepted: November 17, 2023
Article in press: November 17, 2023
Published online: November 28, 2023
Processing time: 51 Days and 15.9 Hours
Abstract
BACKGROUND

Radionuclides produce Cherenkov radiation (CR), which can potentially activate photosensitizers (PSs) in phototherapy. Several groups have studied Cherenkov energy transfer to PSs using optical imaging; however, cost-effectively identifying whether PSs are excited by radionuclide-derived CR and detecting fluorescence emission from excited PSs remain a challenge. Many laboratories face the need for expensive dedicated equipment.

AIM

To cost-effectively confirm whether PSs are excited by radionuclide-derived CR and distinguish fluorescence emission from excited PSs.

METHODS

The absorbance and fluorescence spectra of PSs were measured using a microplate reader and fluorescence spectrometer to examine the photo-physical properties of PSs. To mitigate the need for expensive dedicated equipment and achieve the aim of the study, we developed a method that utilizes a charge-coupled device optical imaging system and appropriate long-pass filters of different wavelengths (manual sequential application of long-pass filters of 515, 580, 645, 700, 750, and 800 nm). Tetrakis (4-carboxyphenyl) porphyrin (TCPP) was utilized as a model PS. Different doses of copper-64 (64CuCl2) (4, 2, and 1 mCi) were used as CR-producing radionuclides. Imaging and data acquisition were performed 0.5 h after sample preparation. Differential image analysis was conducted by using ImageJ software (National Institutes of Health) to visually evaluate TCPP fluorescence.

RESULTS

The maximum absorbance of TCPP was at 390–430 nm, and the emission peak was at 670 nm. The CR and CR-induced TCPP emissions were observed using the optical imaging system and the high-transmittance long-pass filters described above. The emission spectra of TCPP with a peak in the 645–700 nm window were obtained by calculation and subtraction based on the serial signal intensity (total flux) difference between 64CuCl2 + TCPP and 64CuCl2. Moreover, the differential fluorescence images of TCPP were obtained by subtracting the 64CuCl2 image from the 64CuCl2 + TCPP image. The experimental results considering different 64CuCl2 doses showed a dose-dependent trend. These results demonstrate that a bioluminescence imaging device coupled with different long-pass filters and subtraction image processing can confirm the emission spectra and differential fluorescence images of CR-induced TCPP.

CONCLUSION

This simple method identifies the PS fluorescence emission generated by radionuclide-derived CR and can contribute to accelerating the development of Cherenkov energy transfer imaging and the discovery of new PSs.

Keywords: Tetrakis (4-carboxyphenyl) porphyrin; Photosensitizer emission; Radionuclide; Cherenkov radiation; Optical imaging; Long-pass filters

Core Tip: Radionuclides produce Cherenkov radiation (CR), which can potentially activate photosensitizers (PSs) in phototherapy. However, a cost-effective method to determine whether radionuclide-derived CR excites PSs and the measurement of fluorescence emitted by excited PS remain elusive. We propose a cost-effective method using a charge-coupled device optical imaging system combined with long-pass filters and subtraction image processing to distinguish CR and PS fluorescence emission. As a proof-of-concept, 64CuCl2 and the PS tetrakis (4-carboxyphenyl) porphyrin were used in the experiments. This method can contribute to accelerating the development of Cherenkov energy transfer imaging and the discovery of new PSs.