Imaging proliferation in brain tumors with 18F-FLT PET: comparison with 18F-FDG.
Imaging proliferation in brain tumors with 18F-FLT PET: comparison with 18F-FDG.
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发表时间：
2005-06
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通讯作者：
Wei Chen;T. Cloughesy;N. Kamdar;N. Satyamurthy;M. Bergsneider;L. Liau;P. Mischel;J. Czernin;M. P
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作者：
Wei Chen;T. Cloughesy;N. Kamdar;N. Satyamurthy;M. Bergsneider;L. Liau;P. Mischel;J. Czernin;M. P
未标记的3 '-脱氧-3'-（18）F-氟胸苷（（18）F-FLT）是最近开发的PET示踪剂，用于肿瘤细胞增殖成像。我们描述了脑胶质瘤的（18）F-FLT PET，并在相同患者的并行研究中比较了（18）F-FLT和（18）F-FDG PET。方法25例脑胶质瘤患者，采用18F-FLT和18F-FDG进行PET显像。纳入3例长期缓解的稳定患者作为阴性对照受试者。测量了正常脑和肿瘤中的示踪剂动力学。通过标准化摄取值（SUV）和肿瘤与正常组织（T/N）比值定量（18）F-FLT和（18）F-FDG的摄取。比较18F-FLT和18F-FDGPET对新诊断和复发胶质瘤的诊断准确性。超过一半的患者在PET研究后接受了切除术，并检查了PET摄取与Ki-67增殖指数之间的相关性。对患者进行了平均15.4个月（范围：12-20个月）的监测。使用Kaplan-Meier统计分析PET对肿瘤进展和生存的预测能力。结果（18）F-FLT在肿瘤中的摄取迅速，在注射后5-10 min达到峰值，并保持稳定长达75 min。因此，在注射后5 min开始的30 min扫描足以进行成像。（18）F-FLT显示所有高级别（III或IV级）肿瘤。II级肿瘤未显示明显的（18）F-FLT摄取，稳定病变也未显示。（18）F-FLT的绝对摄取较低（最大像素SUV [SUV（max）]，1.33），但图像对比度优于（18）F-FDG（T/N比，3.85 vs 1.49）。（18）5例复发性高级别胶质瘤患者的F-FDG PET检查结果为阴性，这些患者随后在1-3个月内发生肿瘤进展。（18）F-FLT SUV（max）与Ki-67指数的相关性（r = 0.84; P < 0.0001）比（18）F-FDG SUV（max）（r = 0.51; P = 0.07）更强。（18）F-FLT摄取对于肿瘤进展和存活也具有更显著的预测能力（分别为P = 0.0005和P = 0.001）。结论注射后5 min的30 min 18 F-FLT PET比18 F-FDG对复发性高级别肿瘤的成像更敏感，与Ki-67值的相关性更好，是肿瘤进展和生存的更有力的预测因子。因此，（18）F-FLT似乎是一种有前途的示踪剂，可作为高级别胶质瘤增殖的替代标记物。
UNLABELLED 3'-Deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) is a recently developed PET tracer to image tumor cell proliferation. We characterized (18)F-FLT PET of brain gliomas and compared (18)F-FLT with (18)F-FDG PET in side-by-side studies of the same patients. METHODS Twenty-five patients with newly diagnosed or previously treated glioma underwent PET with (18)F-FLT and (18)F-FDG on consecutive days. Three stable patients in long-term remission were included as negative control subjects. Tracer kinetics in normal brain and tumor were measured. Uptake of (18)F-FLT and (18)F-FDG was quantified by the standardized uptake value (SUV) and the tumor-to-normal tissue (T/N) ratio. The accuracy of (18)F-FLT and (18)F-FDG PET in evaluating newly diagnosed and recurrent gliomas was compared. More than half of the patients underwent resection after the PET study and correlations between PET uptake and the Ki-67 proliferation index were examined. Patients were monitored for a mean of 15.4 mo (range, 12-20 mo). The predictive power of PET for tumor progression and survival was analyzed using Kaplan-Meier statistics. RESULTS (18)F-FLT uptake in tumors was rapid, peaking at 5-10 min after injection and remaining stable up to 75 min. Hence, a 30-min scan beginning at 5 min after injection was sufficient for imaging. (18)F-FLT visualized all high-grade (grade III or IV) tumors. Grade II tumor did not show appreciable (18)F-FLT uptake and neither did the stable lesions. The absolute uptake of (18)F-FLT was low (maximum-pixel SUV [SUV(max)], 1.33) but image contrast was better than with (18)F-FDG (T/N ratio, 3.85 vs. 1.49). (18)F-FDG PET studies were negative in 5 patients with recurrent high-grade glioma who subsequently suffered tumor progression within 1-3 mo. (18)F-FLT SUV(max) correlated more strongly with Ki-67 index (r = 0.84; P < 0.0001) than (18)F-FDG SUV(max) (r = 0.51; P = 0.07). (18)F-FLT uptake also had more significant predictive power with respect to tumor progression and survival (P = 0.0005 and P = 0.001, respectively). CONCLUSION Thirty-minute (18)F-FLT PET 5 min after injection was more sensitive than (18)F-FDG to image recurrent high-grade tumors, correlated better with Ki-67 values, and was a more powerful predictor of tumor progression and survival. Thus, (18)F-FLT appears to be a promising tracer as a surrogate marker of proliferation in high-grade gliomas.