글로벌 연구동향
핵의학
- 2021년 04월호
[Sci Rep.] 89Zr anti-CD44 immuno-PET monitors CD44 expression on splenic myeloid cells and HT29 colon cancer cells성균관의대 / 박진원, 정경호, 이경한*
- 출처
- Sci Rep.
- 등재일
- 2021 Feb 16
- 저널이슈번호
- 11(1):3876. doi: 10.1038/s41598-021-83496-3.
- 내용
Abstract
CD44 is a cell-surface glycoprotein involved in cell-cell interaction, adhesion, and migration. CD44 is found on colon cancer cells and on immune cells. Previous studies of 89Zr PET imaging of CD44 have relied on an anti-human antibody (Ab), which can influence biodistribution in murine models. In this study, we used an Ab that cross-reacts with both human and mouse origin CD44 of all isoforms to unveil the type of leukocyte responsible for high splenic anti-CD44 uptake and investigate how its regulation can influence tumor immuno-PET. The Ab was site-specifically labeled with 89Zr-deferoxamine on cysteine residues. 89Zr-anti-CD44 demonstrated high-specific binding to HT29 human colon cancer cells and monocytic cells that showed CD44 expression. When 89Zr-anti-CD44 was administered to Balb/C nude mice, there was remarkably high splenic uptake but low SNU-C5 tumor uptake (1.2 ± 0.7%ID/g). Among cells isolated from Balb/C mouse spleen, there was greater CD44 expression on CD11b positive myeloid cells than lymphocytes. In cultured monocytic and macrophage cells, LPS stimulation upregulated CD44 expression and increased 89Zr-anti-CD44 binding. Similarly, normal Balb/C mice that underwent lipopolysaccharide (LPS) stimulation showed a significant upregulation of CD44 expression on splenic myeloid cells. Furthermore, LPS treatment stimulated a 2.44-fold increase of 89Zr-anti-CD44 accumulation in the spleen, which was attributable to splenic myeloid cells. Finally, in Balb/C nude mice bearing HT29 tumors, we injected 89Zr-anti-CD44 with greater Ab doses to reduce binding to splenic cells. The results showed lower spleen uptake and improved tumor uptake (2.9 ± 1.3%ID/g) with a total of 300 μg of Ab dose, and further reduction of spleen uptake and greater tumor uptake (5.7 ± 0.0%ID/g) with 700 μg Ab dose. Thus, using an 89Zr labeled Ab that cross-reacts with both human and mouse CD44, we demonstrate that CD44 immuno-PET has the capacity to monitor CD44 regulation on splenic myeloid cells and may also be useful for imaging colon tumors.Affiliations
Jin Won Park # 1 , Kyung-Ho Jung # 2 3 , Jin Hee Lee 2 3 , Seung Hwan Moon 2 , Young Seok Cho 2 , Kyung-Han Lee 4 5
1 Scripps Korea Antibody Institute, 1, Kangwondeahak-gil, Chuncheon-si, Gangwon-do, Korea.
2 Department of Nuclear Medicine, Samsung Medical Center, 50 Ilwon-dong, Gangnam-gu, Seoul, Korea.
3 Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University School of Medicine, Seoul, Korea.
4 Department of Nuclear Medicine, Samsung Medical Center, 50 Ilwon-dong, Gangnam-gu, Seoul, Korea. khleenm@naver.com.
5 Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University School of Medicine, Seoul, Korea. khleenm@naver.com.
# Contributed equally.
- 연구소개
- 암과 면역세포의 세포표면 CD44를 표적하는 항체에 site-specific 하게 89Zr 표지한 PET용 probe를 개발하였습니다. LPS에 의해 면역세포가 활성화 될 때 CD44의 발현이 증가하는 것을 대식세포와 마우스 비장 면역세포에서 확인하였고, 89Zr anti-CD44 항체 PET 영상을 통해 살아 있는 마우스 비장내 면역세포에 CD44 발현를 모니터링 할 수 있었습니다. 나아가, CD44 발현이 높은 HT29 마우스 종양모델을 PET 영상할 때 cold 항체의 동시 주사로 probe의 비장섭취를 줄이고 종양 섭취를 항진시킬 수 있음을 확인하였습니다. 결론적으로 89Zr anti-CD44 항체 PET로 면역세포 모니터링과 대장암 영상이 가능함을 규명하였습니다.
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편집위원
Zr-89를 이용한 Immuno PET의 기초 연구로서 추후 인체응용까지 고려 가능한 흥미로운 연구입니다.
덧글달기닫기2021-03-30 11:35:12
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