利用正电子发射断层显像（PET）对肺肿瘤增殖进行成像：18F-氟代胸苷（18F-FLT）与18F-氟代脱氧葡萄糖（18F-FDG）的比较

Imaging proliferation in lung tumors with PET: 18F-FLT versus 18F-FDG.

作者信息

Buck Andreas K, Halter Gisela, Schirrmeister Holger, Kotzerke Jörg, Wurziger Imke, Glatting Gerhard, Mattfeldt Torsten, Neumaier Bernd, Reske Sven N, Hetzel Martin

机构信息

Department of Nuclear Medicine, University of Ulm, Ulm, Germany.

出版信息

J Nucl Med. 2003 Sep;44(9):1426-31.

PMID:12960187

Abstract

UNLABELLED

Recently, the thymidine analog 3'-deoxy-3'-(18)F-fluorothymidine (FLT) was suggested for imaging tumoral proliferation. In this prospective study, we examined whether (18)F-FLT better determines proliferative activity in newly diagnosed lung nodules than does (18)F-FDG.

METHODS

Twenty-six patients with pulmonary nodules on chest CT were examined with PET and the tracers (18)F-FDG and (18)F-FLT. Tumoral uptake was determined by calculation of standardized uptake value (SUV). Within 2 wk, patients underwent resective surgery or had core biopsy. Proliferative activity was estimated by counting nuclei stained with the Ki-67-specific monoclonal antibody MIB-1 per total number of nuclei in representative tissue specimens. The correlation between the percentage of proliferating cells and the SUVs for (18)F-FLT and (18)F-FDG was determined using linear regression analysis.

RESULTS

Eighteen patients had malignant tumors (13 with non-small cell lung cancer [NSCLC], 1 with small cell lung cancer, and 4 with pulmonary metastases from extrapulmonary tumors); 8 had benign lesions. In all visible lesions, mean (18)F-FDG uptake was 4.1 (median, 4.4; SD, 3.0; range, 1.0-10.6), and mean (18)F-FLT uptake was 1.8 (median, 1.2; SD, 2.0; range, 0.8-6.4). Statistical analysis revealed a significantly higher uptake of (18)F-FDG than of (18)F-FLT (Mann-Whitney U test, P < 0.05). (18)F-FLT SUV correlated better with proliferation index (P < 0.0001; r = 0.92) than did (18)F-FDG SUV (P < 0.001; r = 0.59). With the exception of 1 carcinoma in situ, all malignant tumors showed increased (18)F-FDG PET uptake. (18)F-FLT PET was false-negative in the carcinoma in situ, in another NSCLC with a low proliferation index, and in a patient with lung metastases from colorectal cancer. Increased (18)F-FLT uptake was related exclusively to malignant tumors. By contrast, (18)F-FDG PET was false-positive in 4 of 8 patients with benign lesions.

CONCLUSION

(18)F-FLT uptake correlates better with proliferation of lung tumors than does uptake of (18)F-FDG and might be more useful as a selective biomarker for tumor proliferation.

摘要

未标注

最近，有人提出将胸苷类似物3'-脱氧-3'-(18)F-氟胸苷（FLT）用于肿瘤增殖成像。在这项前瞻性研究中，我们检验了(18)F-FLT在确定新诊断的肺结节增殖活性方面是否比(18)F-FDG更具优势。

方法

对26例胸部CT发现有肺结节的患者进行PET检查，并使用示踪剂(18)F-FDG和(18)F-FLT。通过计算标准化摄取值（SUV）来确定肿瘤摄取情况。在2周内，患者接受了切除手术或进行了核心活检。通过对代表性组织标本中用Ki-67特异性单克隆抗体MIB-1染色的细胞核与总细胞核数进行计数，来评估增殖活性。使用线性回归分析确定增殖细胞百分比与(18)F-FLT和(18)F-FDG的SUV之间的相关性。

结果

18例患者患有恶性肿瘤（13例非小细胞肺癌[NSCLC]，1例小细胞肺癌，4例肺外肿瘤肺转移）；8例有良性病变。在所有可见病变中，(18)F-FDG的平均摄取量为4.1（中位数，4.4；标准差，3.0；范围，1.0 - 10.6），(18)F-FLT的平均摄取量为1.8（中位数，1.2；标准差，2.0；范围，0.8 - 6.4）。统计分析显示，(18)F-FDG的摄取量显著高于(18)F-FLT（曼-惠特尼U检验，P < 0.05）。与(18)F-FDG的SUV相比，(18)F-FLT的SUV与增殖指数之间的相关性更好（P < 0.0001；r = 0.92），而(18)F-FDG的SUV与增殖指数的相关性为P < 0.001；r = 0.59。除1例原位癌外，所有恶性肿瘤的(18)F-FDG PET摄取均增加。(18)F-FLT PET在原位癌、另1例增殖指数较低的NSCLC以及1例结直肠癌肺转移患者中呈假阴性。(18)F-FLT摄取增加仅与恶性肿瘤有关。相比之下，8例良性病变患者中有4例(18)F-FDG PET呈假阳性。