Department of Radiology and Nuclear Medicine, University of Tuebingen, Tuebingen, Germany.
J Nucl Med. 2010 Jun;51(6):845-53. doi: 10.2967/jnumed.109.070425. Epub 2010 May 19.
Because (18)F-FDG PET alone has only limited value in metastatic germ cell tumors (GCTs), we investigated the addition of 3'-deoxy-3'-(18)F-fluorothymidine (FLT) to (18)F-FDG for early response monitoring and prediction of the histology of residual tumor masses in patients with metastatic GCT.
Eleven patients with metastatic GCT were examined with both (18)F-FDG PET/CT and (18)F-FLT PET/CT before chemotherapy, after the first cycle of chemotherapy (early response), and 3 wk after completion of chemotherapy. In 1 patient with negative (18)F-FLT PET/CT results before chemotherapy, no further (18)F-FLT scanning was performed. PET images were analyzed visually and, using standardized uptake values (SUVs), semiquantitatively. The results were compared with the findings of CT and tumor marker levels and validated by histopathologic examination of resected residual masses, including Ki-67 immunostaining (7 patients), or by clinicoradiologic follow-up for at least 6 mo (4 patients). A responder was defined as a patient showing the presence of necrosis, a complete remission, or a marker-negative partial remission within a minimum progression-free interval of 6 mo. Early treatment response was judged according to the criteria of the European Organization for Research and Treatment of Cancer.
Before chemotherapy, reference lesions showed increased (18)F-FDG uptake (mean SUV, 8.8; range, 2.9-15.0) in all patients and moderate (18)F-FLT uptake (mean SUV, 3.7; range, 1.7-9.7) in 10 of 11 patients. After 1 cycle of chemotherapy, mean SUV decreased in responders and nonresponders by 64% and 60%, respectively, for (18)F-FDG (P = 0.8) and by 58% and 48%, respectively, for (18)F-FLT (P = 0.5). After the end of chemotherapy, mean SUV decreased in responders and nonresponders by 85% and 73%, respectively, for (18)F-FDG (P = 0.1) and by 68% and 65%, respectively, for (18)F-FLT (P = 0.8). The results of early and final PET were inconsistent in 6 of 11 patients for (18)F-FDG and in 4 of 10 patients for (18)F-FLT. Both patients with teratoma had false-negative results on both (18)F-FDG and (18)F-FLT. The sensitivity, specificity, positive predictive value, and negative predictive value for detection of viable tumor after 1 cycle of chemotherapy were 60%, 33%, 43%, and 50%, respectively, for (18)F-FDG and 60%, 80%, 75%, and 67%, respectively, for (18)F-FLT PET/CT. The respective values after the end of chemotherapy were 20%, 100%, 100%, and 60% for (18)F-FDG and 0%, 100%, 0%, and 50% for (18)F-FLT PET/CT.
PET-negative residual masses after chemotherapy of metastatic GCT still require resection, since the low negative predictive value of (18)F-FDG PET for viable tumor cannot be improved by application of (18)F-FLT.
由于(18)F-FDG PET 在转移性生殖细胞瘤(GCT)中的应用价值有限,我们研究了在化疗前、化疗第一周期后(早期反应)和化疗结束后 3 周,将 3'-脱氧-3'-(18)F-氟胸苷(FLT)加入(18)F-FDG 对转移性 GCT 患者残留肿瘤的组织学进行早期反应监测和预测。
11 例转移性 GCT 患者在化疗前、化疗第一周期后、化疗结束后 3 周分别行(18)F-FDG PET/CT 和(18)F-FLT PET/CT 检查。在 1 例化疗前(18)F-FLT PET/CT 结果阴性的患者中,未进行进一步的(18)F-FLT 扫描。PET 图像采用视觉和标准化摄取值(SUV)进行分析。结果与 CT 和肿瘤标志物水平进行比较,并通过切除的残留肿瘤组织的组织病理学检查(包括 Ki-67 免疫组化检查,7 例)或至少 6 个月的临床影像学随访(4 例)进行验证。根据欧洲癌症研究与治疗组织的标准,将缓解患者定义为在至少 6 个月的无进展间期内出现坏死、完全缓解或标志物阴性部分缓解的患者。早期治疗反应根据欧洲癌症研究与治疗组织的标准进行判断。
化疗前,参考病变在所有患者中均显示(18)F-FDG 摄取增加(平均 SUV,8.8;范围,2.9-15.0),在 11 例患者中的 10 例中显示中度(18)F-FLT 摄取(平均 SUV,3.7;范围,1.7-9.7)。在化疗第 1 周期后,应答者和无应答者的(18)F-FDG SUV 分别降低 64%和 60%(P=0.8),(18)F-FLT SUV 分别降低 58%和 48%(P=0.5)。化疗结束后,应答者和无应答者的(18)F-FDG SUV 分别降低 85%和 73%(P=0.1),(18)F-FLT SUV 分别降低 68%和 65%(P=0.8)。在 11 例患者中的 6 例和 10 例患者中的 4 例,(18)F-FDG 和(18)F-FLT 的早期和最终 PET 结果不一致。2 例含有畸胎瘤的患者(18)F-FDG 和(18)F-FLT 均呈假阴性结果。化疗第 1 周期后检测存活肿瘤的敏感性、特异性、阳性预测值和阴性预测值分别为(18)F-FDG 为 60%、33%、43%和 50%,(18)F-FLT PET/CT 为 60%、80%、75%和 67%。化疗结束后,(18)F-FDG 的分别为 20%、100%、100%和 60%,(18)F-FLT PET/CT 的分别为 0%、100%、0%和 50%。
转移性 GCT 化疗后(18)F-FDG PET 阴性的残留肿瘤仍需切除,因为(18)F-FDG 对存活肿瘤的低阴性预测值不能通过应用(18)F-FLT 来提高。