KIRAMS, KIST / 조지훈, 강지수*, 김세훈*
Abstract
Photodynamic therapy (PDT) is an effective cancer treatment option, but it suffers from penetration limit of light, making it available only for superficial and endoscopically accessible cancers. Recently, there have been reports that Cerenkov luminescence originated from radioisotopes can be utilized as an excitation source for PDT without external light illumination. Here, cancer-selective agents, i.e., (1) clinically available 5-aminolevulinic acid (5-ALA), which promotes cancer metabolism-specific accumulation of protoporphyrin IX (PpIX), and (2) 64Cu-DOTA-trastuzumab, which has HER2-expressing cancer selective uptake, are separately applied as a photosensitizer and an in situ radiator, respectively, to potentiate tumor-specific Cerenkov luminescence energy transfer (CLET) from 64Cu to PpIX for high-precision PDT of cancer. It is shown that the combinational administration and tumor colocalization of 5-ALA and 64Cu-DOTA-trastuzumab exert significant in vitro cytotoxicity (cell viability <9%) as well as in vivo antitumor effects (tumor volume ratio of 0.50 on 14 days post-injection) on HER2-expressing breast and gastric cancer models. This study proves that high-precision treatment regimen using dual-targeted CLET-based PDT is feasible for HER2-expressing cancers. Furthermore, the results offer great potential for clinical translation to the dual-targeted CLET-based PDT because the treatment regimen uses components, 5-ALA and 64Cu-DOTA-trastuzumab, which are already in clinical uses.
Affiliations
Chihoon Jo 1, Heesu Ahn 2, Ji Hwan Kim 1, Yong Jin Lee 2, Jung Young Kim 2, Kyo Chul Lee 2, Chi Soo Kang 3, Sehoon Kim 4
1145 Anam-ro, Seongbuk-gu, KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul 02841, Republic of Korea; 5 Hwarang-ro 14-gil, Seongbuk-gu, Chemical and Biological Integrative Research Center, Korea Institute of Science and Technology, Seoul 02792, Republic of Korea.
275 Nowon-ro, Nowon-gu, Division of Applied RI, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Republic of Korea.
375 Nowon-ro, Nowon-gu, Division of Applied RI, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Republic of Korea. Electronic address: cskang0224@kirams.re.kr.
4145 Anam-ro, Seongbuk-gu, KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul 02841, Republic of Korea; 5 Hwarang-ro 14-gil, Seongbuk-gu, Chemical and Biological Integrative Research Center, Korea Institute of Science and Technology, Seoul 02792, Republic of Korea. Electronic address: sehoonkim@kist.re.kr.