CAJ | 학술논문

背景与目的：诱导细胞凋亡是肿瘤化疗的机制之一，分子影像能在活体内无创、动态地检测细胞凋亡，有助于药物筛选和疗效分析。本研究旨在探讨N-琥珀酰亚胺-4-氟苯甲酸酯偶联的氟-18-膜联蛋白B1(18F-SFB-AnnexinB1)显像剂早期评价化疗诱导细胞凋亡的可行性。方法：以SFB作为中间体将18F标记到AnnexinB1上。了解18F-SFB-Annexin B1在健康小鼠体内的生物分布特性。建立Walker-256荷瘤小鼠模型，随机分为两组，化疗组腹腔注射环磷酰胺(CTX 200 mg/kg，n=3)，对照组注射等体积无菌0.9%的氯化钠溶液(n=3)。24 h后静脉注射18F-SFB-Annexin B1，分别于注射后1、2、3、4 h进行PET/CT显像。比较肿瘤/肌肉放射性摄取率比值(T/M)与原位缺口末端标记(TUNEL)染色法测定凋亡指数(AI)的关系。结果：18F-SFB-Annexin B1放化纯度>95%，生物分布显示肾脏放射性最高，其次为肝、脾和心肌，显像剂在体内清除速率快。化疗组与对照组各时间点T/M比值分别为4.38±0.56、6.75±1.16、6.44±1.12、4.81±0.17和2.35±0.14、2.99±0.55、3.04±0.41、2.33±0.47，差异有统计学意义(F分别为23.790、16.913、14.046、77.517，P均<0.05)。TUNEL染色AI分别为(21.00±0.04)%和(8.58±0.01)%，差异有统计学意义(F=21.539，P<0.05)，且T/M值与AI间有很好的相关性(r=0.91，P<0.05)。结论：18F-SFB-AnnexinB1能早期反映化疗诱导的细胞凋亡，有望用于活体细胞凋亡分子显像和早期疗效判断。
배경여목적：유도세포조망시종류화료적궤제지일，분자영상능재활체내무창、동태지검측세포조망，유조우약물사선화료효분석。본연구지재탐토N-호박선아알-4-불분갑산지우련적불-18-막련단백B1(18F-SFB-AnnexinB1)현상제조기평개화료유도세포조망적가행성。방법：이SFB작위중간체장18F표기도AnnexinB1상。료해18F-SFB-Annexin B1재건강소서체내적생물분포특성。건립Walker-256하류소서모형，수궤분위량조，화료조복강주사배린선알(CTX 200 mg/kg，n=3)，대조조주사등체적무균0.9%적록화납용액(n=3)。24 h후정맥주사18F-SFB-Annexin B1，분별우주사후1、2、3、4 h진행PET/CT현상。비교종류/기육방사성섭취솔비치(T/M)여원위결구말단표기(TUNEL)염색법측정조망지수(AI)적관계。결과：18F-SFB-Annexin B1방화순도>95%，생물분포현시신장방사성최고，기차위간、비화심기，현상제재체내청제속솔쾌。화료조여대조조각시간점T/M비치분별위4.38±0.56、6.75±1.16、6.44±1.12、4.81±0.17화2.35±0.14、2.99±0.55、3.04±0.41、2.33±0.47，차이유통계학의의(F분별위23.790、16.913、14.046、77.517，P균<0.05)。TUNEL염색AI분별위(21.00±0.04)%화(8.58±0.01)%，차이유통계학의의(F=21.539，P<0.05)，차T/M치여AI간유흔호적상관성(r=0.91，P<0.05)。결론：18F-SFB-AnnexinB1능조기반영화료유도적세포조망，유망용우활체세포조망분자현상화조기료효판단。
Background and purpose: One of the main mechanism of chemotherapy is inducing tuomr apoptosis. Molecular imaging can allow noninvasively and dynamically monitor tumor apoptosis in vivo, and help to drug screening and therapeutic evaluation. The purpose of this study was to evaluate the feasibility of 18F-SFB-Annexin B1 in detecting apoptosis at an early phase after chemotheraphy. Methods:Annexin B1 was labeled with 18F using SFB as a chelating agent. Tissue distribution of 18F-SFB-Annexin B1 was studied in healthy mice by the dissection method. W256 tumor-bearing rats were injected with 18F-SFB-Annexin B1 intravenously at 24 h after the treatment of cyclophosphamide (CTX 200 mg/kg) or saline. Then imaging was acquired at 1, 2, 3, and 4 h postinjection on a PET/CT, and the tumor-to-muscle ratio of SUVmax (T/M) and the AI from TUNEL testing were compared. Results: 18F-SFB-Annexin B1 had a radiochemical pruity (RCP)>95%. Biodistribution of this probe showed a predominant uptake in the kidney, then was liver, spleen, and myocardium, rapid clearance from blood and urinary was observed. The radios of T/M were 4.38±0.56, 6.75±1.16, 6.44±1.12, 4.81±0.17, respectively at 1, 2, 3, 4 h post injection of the chemotherapy group, much higher than that of the saline group (2.35±0.14, 2.99±0.55, 3.04±0.41, 2.33±0.47, respectively). The differences between the two groups were significant (F=23.790, 16.913, 14.046, 77.517, respectively, all P<0.05). TUNEL staining revealed that chemotherapy treatment significantly increased the percentage of apoptosis cells with an AI of (21.00±0.04)%in the chemotherapy group, higher than that in the saline group (8.58±0.01)%, the difference was significant (F=21.539, P<0.05). The radios of T/M were significantly correlated with the values of AI (r=0.91, P<0.05). Conclusion: 18F-SFB-Annexin B1 can be used to apoptosis imaging and early therapeutic evaluation in vivo because it can reflect apoptosis at an early stage after chemotheraphy.