Division of Nuclear Medicine, Department of Radiology, National Center for Global Health and Medicine, Tokyo, Japan.
J Nucl Med. 2012 Feb;53(2):199-206. doi: 10.2967/jnumed.111.095539. Epub 2011 Dec 21.
A new tracer, 4'-[methyl-(11)C]-thiothymidine ((11)C-4DST), has been developed as an in vivo cell proliferation marker based on the DNA incorporation method. This study evaluated the potential of (11)C-4DST PET/CT for imaging proliferation in non-small cell lung cancer (NSCLC), compared with (18)F-FDG PET/CT.
Eighteen patients with lung lesions were examined by PET/CT using (11)C-4DST and (18)F-FDG. We constructed decay-corrected time-activity curves of 9 major regions as the mean standardized uptake value. We then compared the maximum standardized uptake value (SUVmax) of lung tumors on both (11)C-4DST and (18)F-FDG PET/CT with the Ki-67 index of cellular proliferation and with CD31-positive vessels as a marker of angiogenesis in surgical pathology.
NSCLC was pathologically confirmed in 19 lesions of 18 patients. Physiologic accumulation of (11)C-4DST was high in liver, kidney, and bone marrow and low in aorta, brain, lung, and myocardium. Biodistribution of (11)C-4DST was almost stable by 20 min after injection of (11)C-4DST. Mean (11)C-4DST SUVmax for lung cancer was 2.9 ± 1.0 (range, 1.5-4.7), significantly different from mean (18)F-FDG SUVmax, which was 6.2 ± 4.5 (range, 0.9-17.3; P < 0.001). The correlation coefficient between SUVmax and Ki-67 index was higher with (11)C-4DST (r = 0.82) than with (18)F-FDG (r = 0.71). The correlation coefficient between SUVmax and CD31 was low with both (11)C-4DST (r = 0.21) and (18)F-FDG (r = 0.21), showing no significant difference between the tracers.
A higher correlation with proliferation of lung tumors was seen for (11)C-4DST than for (18)F-FDG. (11)C-4DST PET/CT may allow noninvasive imaging of DNA synthesis in NSCLC.
基于 DNA 掺入法，开发一种新的示踪剂 4'-[甲基-(11)C]-硫代胸苷((11)C-4DST)，作为体内细胞增殖的标记物。本研究评估了 (11)C-4DST PET/CT 对非小细胞肺癌(NSCLC)增殖成像的潜力，并与 (18)F-FDG PET/CT 进行了比较。
18 例肺部病变患者分别行 (11)C-4DST 和 (18)F-FDG PET/CT 检查。我们构建了 9 个主要区域的衰减校正时间-活性曲线，作为平均标准化摄取值。然后，我们将肺肿瘤的最大标准化摄取值(SUVmax)与细胞增殖的 Ki-67 指数以及手术病理中 CD31 阳性血管作为血管生成的标志物进行比较。
18 例患者的 19 个病变经病理证实为 NSCLC。(11)C-4DST 在肝脏、肾脏和骨髓中的生理性摄取较高，而在主动脉、大脑、肺和心肌中的摄取较低。注射 (11)C-4DST 20 min 后，(11)C-4DST 的生物分布基本稳定。肺癌的平均 (11)C-4DST SUVmax 为 2.9±1.0(范围，1.5-4.7)，显著低于平均 (18)F-FDG SUVmax(6.2±4.5，范围，0.9-17.3；P<0.001)。SUVmax 与 Ki-67 指数的相关系数用 (11)C-4DST 测量时更高(r=0.82)，而用 (18)F-FDG 测量时更低(r=0.71)。SUVmax 与 CD31 的相关系数用 (11)C-4DST(r=0.21)和 (18)F-FDG(r=0.21)测量时均较低，两种示踪剂之间无显著差异。
与 (18)F-FDG 相比，(11)C-4DST 与肺癌肿瘤的增殖相关性更高。(11)C-4DST PET/CT 可能允许对 NSCLC 中的 DNA 合成进行非侵入性成像。
