KIRAMS / 안희수, 이용진*
Abstract
Early diagnosis of radiation-induced pulmonary fibrosis (RIPF) in lung cancer patients after radiation therapy is important. A gastrin-releasing peptide receptor (GRPR) mediates the inflammation and fibrosis after irradiation in mice lungs. Previously, our group synthesized a GRPR-targeted positron emission tomography (PET) imaging probe, [64Cu]Cu-NODAGA-galacto-bombesin (BBN), an analogue peptide of GRP. In this study, we evaluated the usefulness of [64Cu]Cu-NODAGA-galacto-BBN for the early prediction of RIPF. We prepared RIPF mice and acquired PET/CT images of [18F]F-FDG and [64Cu]Cu-NODAGA-galacto-BBN at 0, 2, 5, and 11 weeks after irradiation (n = 3-10). We confirmed that [64Cu]Cu-NODAGA-galacto-BBN targets GRPR in irradiated RAW 264.7 cells. In addition, we examined whether [64Cu]Cu-NODAGA-galacto-BBN monitors the therapeutic efficacy in RIPF mice (n = 4). As a result, the lung uptake ratio (irradiated-to-normal) of [64Cu]Cu-NODAGA-galacto-BBN was the highest at 2 weeks, followed by its decrease at 5 and 11 weeks after irradiation, which matched with the expression of GRPR and was more accurately predicted than [18F]F-FDG. These uptake results were also confirmed by the cell uptake assay. Furthermore, [64Cu]Cu-NODAGA-galacto-BBN could monitor the therapeutic efficacy of pirfenidone in RIPF mice. We conclude that [64Cu]Cu-NODAGA-galacto-BBN is a novel PET imaging probe for the early prediction of RIPF-targeting GRPR expressed during the inflammatory response.
Affiliations
Heesu Ahn 1, Ji-Hee Kim 2, Kyo Chul Lee 1, Ji-Ae Park 1, Jung Young Kim 1, Yoon-Jin Lee 2, Yong Jin Lee 1
1Division of Applied RI, Korea Institute of Radiological and Medical Sciences, Seoul 01812, South Korea.
2Division of Radiation Biomedical, Korea Institute of Radiological and Medical Sciences, Seoul 01812, South Korea.
편집위원
폐암 환자 치료에 있어 방사선 치료 후 발생할 수 있는 방사선 유발 폐 섬유증 (radiation-induced pulmonary fibrosis; RIPF)의 조기 진단은 중요하다. 가스트린 방출 펩타이드 수용체 (gastrin-releasing peptide receptor; GRPR)는 방사선 조사 후 폐의 염증과 섬유증을 유발시킬 수 있다. 본 연구진은 GRP의 아날로그 펩타이드인 [64Cu]Cu-NODAGA-galacto-bombesin(BBN)이라는 GRPR PET 영상 프로브를 합성하여 RIPF의 조기 예측을 실시하였고, 염증 반응 동안 발현되는 RIPF의 예측 결과를 보여주었다.
2023-02-06 15:54:23