Liu Xi, Zhou Nai-Kang, Zhang Jin-Ming, Liang Zhao-Yang, Zheng Xin
Department of Thoracic Surgery, General Hospital of PLA, Beijing, 100853 P. R. China.
Ai Zheng. 2006 Dec;25(12):1512-6.
BACKGROUND & OBJECTIVE: 3'-Deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) has been described recently as a new positron emission tomography (PET) tracer for imaging tumor cell proliferation. This study was to investigate the biodistribution and PET imaging of (18)F-FLT in a murine model of lung cancer, and to explore the correlation of (18)F-FLT uptake to cell proliferation of lung cancer.
A total of 48 T739 mice bearing lung adeno-carcinoma were randomized into (18)F-FLT group and 2-(18)F-fluoro-2-deoxy-D-glucose ((18)F-FDG) group according to the radioactive tracers. Each group was also divided into 3 subgroups: (A) untreated controls, (B) 1 day after treatment of cisplatin, (C) 2 days after treatment of cisplatin. Each subgroup contained 8 mice. All mice were injected with (18)F-FLT or (18)F-FDG through the tail veins. The biodistribution of (18)F-FLT and (18)F-FDG in tumor tissue was measured with well-gamma detector 60 min after injection; the PET imaging of mice was performed. Tumor cell proliferation was determined by immunohistochemical examination of proliferating cell nuclear antigen (PCNA).
In both subgroups A, the PET images of the tracers in tumor were clear. Considerable radioactive uptake of tumor was observed; the T/NT ratios of tumor/blood, tumor/muscle and tumor/lung were all above 2.0. The positive rate of PCNA was reduced significantly in (18)F-FLT group after treatment of cisplatin [(90.3+/-3.9)% (A) vs. (65.5+/-9.2)% (B) and (47.4+/-7.2)% (C), P<0.01], and in (18)F-FDG group [(91.2+/-3.5)% (A) vs. (67.8+/-8.2)% (B) and (45.9+/-9.1)% (C), P<0.01]. Tumor uptake of (18)F-FLT was decreased rapidly after treatment [(1.25+/-0.19) %ID/g (A) vs. (0.82+/-0.19) %ID/g (B) and (0.37+/-0.17) %ID/g (C), P<0.01]; tumor uptake of (18)F-FDG was decreased slightly after treatment [(8.83+/-1.73)%ID/g (A) vs. (7.88+/-1.78)% ID/g (B) and (7.45+/-1.67)%ID/g (C), P>0.05]. The PET imaging confirmed that tumor (18)F-FLT retention was suppressed after treatment. Tumor uptake of (18)F-FLT was correlated to the positive rate of PCNA (r=0.930, P<0.001), but tumor uptake of (18)F-FDG did not (r=-0.136, P=0.538).
The uptake of (18)F-FLT in lung malignant tissues is higher than that in normal tissues, therefore, the tumor could be imaged clearly with PET. The correlation of tumor uptake of (18)F-FLT to PCNA expression is more obvious than that of (18)F-FDG. (18)F-FLT is a promising PET tracer for reflecting cell proliferation in lung carcinoma.
3'-脱氧-3'-(18)F-氟胸苷((18)F-FLT)最近被描述为一种用于肿瘤细胞增殖成像的新型正电子发射断层显像(PET)示踪剂。本研究旨在探讨(18)F-FLT在小鼠肺癌模型中的生物分布及PET显像，并探讨(18)F-FLT摄取与肺癌细胞增殖的相关性。
将48只荷肺腺癌的T739小鼠按放射性示踪剂随机分为(18)F-FLT组和2-(18)F-氟-2-脱氧-D-葡萄糖((18)F-FDG)组。每组又分为3个亚组：(A)未治疗对照组；(B)顺铂治疗后1天；(C)顺铂治疗后2天。每个亚组包含8只小鼠。所有小鼠均经尾静脉注射(18)F-FLT或(18)F-FDG。注射后60分钟用井型γ探测器测量(18)F-FLT和(18)F-FDG在肿瘤组织中的生物分布；对小鼠进行PET显像。通过增殖细胞核抗原(PCNA)免疫组化检查确定肿瘤细胞增殖情况。
在两个A亚组中，示踪剂在肿瘤中的PET图像均清晰。观察到肿瘤有明显的放射性摄取；肿瘤/血液、肿瘤/肌肉和肿瘤/肺的T/NT比值均高于2.0。顺铂治疗后(18)F-FLT组PCNA阳性率显著降低[(A组(90.3±3.9)% vs. B组(65.5±9.2)%和C组(47.4±7.2)%, P<0.01]，(18)F-FDG组也如此[(A组(91.2±3.5)% vs. B组(67.8±8.2)%和C组(45.9±9.1)%, P<0.01]。治疗后(18)F-FLT的肿瘤摄取迅速降低[(A组(1.25±0.19)%ID/g vs. B组(0.82±0.19)%ID/g和C组(0.37±0.17)%ID/g, P<0.01]；(18)F-FDG的肿瘤摄取治疗后略有降低[(A组(8.83±1.73)%ID/g vs. B组(7.88±1.78)%ID/g和C组(7.45±1.67)%ID/g, P>0.05]。PET显像证实治疗后肿瘤(18)F-FLT滞留受到抑制。(18)F-FLT的肿瘤摄取与PCNA阳性率相关(r=0.9, P<0.001)，但(18)F-FDG的肿瘤摄取无相关性(r=-0.136, P=0.538)。
(18)F-FLT在肺恶性组织中的摄取高于正常组织，因此，PET可清晰显示肿瘤。(18)F-FLT的肿瘤摄取与PCNA表达的相关性比(18)F-FDG更明显。(18)F-FLT是一种有前景的反映肺癌细胞增殖的PET示踪剂。
