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First in human evaluation of a newly developed integrin binding positron emission tomography tracer, 18F-RGD-K5 : comparison with 18F-FDG uptake pattern and microvessel density in patients with breast cancer

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 유방암 환자에서 새로운 integrin 결합 양전자방출단층촬영 추적자, 18F-RGD-K5의 최초 임상 시험: 18F-FDG 섭취 및 미세혈관농도와의 비교 
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Dept. of Medicine/석사
The purpose of this study was to evaluate the biodistribution and dosimetry of a newly developed integrin binding agent, 18F-RGD-K5, in healthy volunteers, and to compare the uptake pattern of 18F-RGD-K5 with 18F-FDG and microvessel density (MVD) in tumor specimen in patients with breast cancer. Methods: Four female healthy volunteers underwent five successive dynamic 18F-RGD-K5 PET scans and radiation absorbed doses were calculated. Eleven patients with primary or metastatic breast cancer underwent 18F-FDG and 18F-RGD-K5 PET scans. Biopsy specimen was obtained in 9 patients and immunohistochemistry using a mouse monoclonal antibody against CD31 was performed. In vitro 18F-FDG and 18F-RGD-K5 uptake and western blot analysis in breast cancer cell lines MCF-7 and MDA-MB-231 were also examined. Results: The radiation dose from 18F-RGD-K5 is similar to the dose from 18F-FDG and other 18F-based imaging agents. In 11 patients, a total of 189 lesions were identified on 18F-FDG PET scan, and 166 lesions (87.8%) showed increased 18F-RGD-K5 uptake. In comparison with 18F-RGD-K5 uptake, 18F-FDG uptake was higher in 108 lesions, and similar in 56 lesions. In 2 lesions, however, 18F-RGD-K5 uptake was higher. Although statistically insignificant, a weak correlation was observed between SUVs of 18F-RGD-K5 and MVD (r=0.43; P=0.25). No correlation was found between SUVs of 18F-RGD-K5 and 18F-FDG, or microvessel area. In vitro experiments showed that integrin β3 protein was more highly expressed in more aggressive MDA-MB-231 cells than in MCF-7 cells. However, 18F-RGD-K5 uptake was higher in MCF-7 cells than in MDA-MB-231 cells. These data suggest that 18F-RGD-K5 might recognize not only integrin αvβ3 but also other integrin subtypes, or a subpopulation of integrin αvβ3. Conclusion: Although 18F-RGD-K5 uptake was not well correlated with MVD, it is a safe and useful marker for noninvasive visualization of integrin expression in patients with breast cancer.
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Yonsei Authors
Cho, Hojin(조호진) ORCID logo https://orcid.org/0000-0002-8686-172X
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