CAJ | 학술논문

　　背景与目的：整合素αvβ3受体在促进、维持以及调节血管生成的过程中有着至关重要的作用，高表达于多种肿瘤细胞及新生血管内皮细胞。RGD多肽序列可与整合素αvβ3受体特异性结合，有助于评价肿瘤的生长状况和侵袭性。本实验主要研究18F标记的RGD二聚体18F-E[c(RGDfK)2]在正常昆明小鼠体内的生物分布和荷人神经胶质瘤裸鼠模型的小动物PET/CT显像情况。方法：以硝基RGD二聚体4-NO2-3-TFMBz-E [c(RGDfK)2]为前体，使用改进的自动化合成模块Explora GN，一步法直接标记合成18F-E[c(RGDfK)2]。用昆明小鼠分析18F-E[c(RGDfK)2]0.5、1、2、4 h的生物分布，计算每克组织放射性占注入量的百分比(%ID/g)。观察荷人神经胶质瘤裸鼠模型1、2、4 h的小动物PET/CT显像情况。结果：18F-E[c(RGDfK)2]的标记率约为10%，放化纯度＞98%，稳定性可达10 h。18F-E[c(RGDfK)2]主要经肾排泄，血液清除迅速，注射后1 h，肾、肝、小肠、肌肉和血的放射性摄取值分别为(1.02±0.16)%ID/g、(0.24±0.06)%ID/g、(0.35±0.03)%ID/g、(0.13±0.03)%ID/g和(0.11±0.03)%ID/g。注射后1 h，肿瘤对18F-E[c(RGDfK)2]的摄取达到高峰(5.2±0.56)%ID/g，T/M为5.36。阻断显像中，可见肿瘤组织放射性摄取明显减低，T/M平均值为1.57。结论：18F-E[c(RGDfK)2]与整合素受体特异性结合，肿瘤摄取较高、显像清晰，可用于整合素表达阳性肿瘤的预后判断、血管靶向治疗适应证的选择及疗效判断。
　　배경여목적：정합소αvβ3수체재촉진、유지이급조절혈관생성적과정중유착지관중요적작용，고표체우다충종류세포급신생혈관내피세포。RGD다태서렬가여정합소αvβ3수체특이성결합，유조우평개종류적생장상황화침습성。본실험주요연구18F표기적RGD이취체18F-E[c(RGDfK)2]재정상곤명소서체내적생물분포화하인신경효질류라서모형적소동물PET/CT현상정황。방법：이초기RGD이취체4-NO2-3-TFMBz-E [c(RGDfK)2]위전체，사용개진적자동화합성모괴Explora GN，일보법직접표기합성18F-E[c(RGDfK)2]。용곤명소서분석18F-E[c(RGDfK)2]0.5、1、2、4 h적생물분포，계산매극조직방사성점주입량적백분비(%ID/g)。관찰하인신경효질류라서모형1、2、4 h적소동물PET/CT현상정황。결과：18F-E[c(RGDfK)2]적표기솔약위10%，방화순도＞98%，은정성가체10 h。18F-E[c(RGDfK)2]주요경신배설，혈액청제신속，주사후1 h，신、간、소장、기육화혈적방사성섭취치분별위(1.02±0.16)%ID/g、(0.24±0.06)%ID/g、(0.35±0.03)%ID/g、(0.13±0.03)%ID/g화(0.11±0.03)%ID/g。주사후1 h，종류대18F-E[c(RGDfK)2]적섭취체도고봉(5.2±0.56)%ID/g，T/M위5.36。조단현상중，가견종류조직방사성섭취명현감저，T/M평균치위1.57。결론：18F-E[c(RGDfK)2]여정합소수체특이성결합，종류섭취교고、현상청석，가용우정합소표체양성종류적예후판단、혈관파향치료괄응증적선택급료효판단。
Background and purpose:Integrinαvβ3 receptor plays an important role in promoting, sustaining and regulating the angiogenesis. It is overexpressed on neovascular endothelial cells and tumor cells. RGD peptide specifically binds to integrinαvβ3, which could evaluate growth status and invasiveness of tumor. This study aimed to investigate the biodistribution in healthy KM mice and micro PET/CT imaging in U87MG tumor-bearing mice of 18F-E[c(RGDfK)2]. Methods: 18F-E[c(RGDfK)2] was produced using an automated synthesis module via a simple one-step 18F-labeling strategy of the precursor 4-NO2-3-TFMBz-E[c(RGDfK)2]. The percentage activity of injection dose per gram of tissue (%ID/g) was calculated at 0.5, 1, 2, 4 h post injection of the probe. Micro PET/CT images of U87MG tumor-bearing nude mice with or without 18F-E[c(RGDfK)2] blocking were acquired at each time point. Results: The labeling efficiency and radiochemical purity of 18F-E[c(RGDfK)2] were 10% and 98%, respectively. 18F-E[c(RGDfK)2] was excreted via renal route, with a high blood clearance. The other organs had background-level activity accumulation. At 1 h, the%ID/g of kidney, liver, intestine, muscle and blood was (1.02±0.16)%ID/g,(0.24±0.06)%ID/g, (0.35±0.03)%ID/g, (0.13±0.03)%ID/g and (0.11±0.03)%ID/g 18F-E[c(RGDfK)2] had initial high tumor uptake [(5.2±0.56)%ID/g] and good tumor-to-background contrast (5.36) at 1 h post injection. Tumor uptake for blocking group was lower than those without blocking, and T/M reduced to 1.57. Conclusion: 18F-E[c(RGDfK)2] appears a promising PET molecular imaging probe targeting integrin αvβ3, with high tumor uptake. It could be suitable for prognosis evaluation of integrin-positive tumor, selection of vascular targeting therapy and therapy effect monitoring.