Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
PLoS One. 2013 May 24;8(5):e63705. doi: 10.1371/journal.pone.0063705. Print 2013.
Pemetrexed is a thymidylate synthase (TS) inhibitor and is effective in non-small cell lung cancer (NSCLC). 3'-deoxy-3'-[¹⁸F]fluorothymidine (¹⁸F-FLT), a proliferation marker, could potentially identify tumor specific TS-inhibition. The aim of this study was to investigate the effect of pemetrexed-induced TS-inhibition on ¹⁸F-FLT uptake 4 hours after pemetrexed administration in metastatic NSCLC patients.
Fourteen NSCLC patients underwent dynamic ¹⁸F-FLT positron emission tomography (PET) scans at baseline and 4 hours after the first dose of pemetrexed. Volumes of interest were defined with a 41%, 50% and 70% threshold of the maximum pixel. Kinetic analysis and simplified measures were performed. At one, two, four and six hours after pemetrexed, plasma deoxyuridine was measured as systemic indicator of TS-inhibition. Tumor response measured with response evaluation criteria in solid tumors (RECIST), time to progression (TTP) and overall survival (OS) were determined.
Eleven patients had evaluable ¹⁸F-FLT PET scans at baseline and 4 hours after pemetrexed. Two patients had increased ¹⁸F-FLT uptake of 35% and 31% after pemetrexed, whereas two other patients had decreased uptake of 31%. In the remaining seven patients ¹⁸F-FLT uptake did not change beyond test-retest borders. In all patients deoxyuridine levels raised after administration of pemetrexed, implicating pemetrexed-induced TS-inhibition. ¹⁸F-FLT uptake in bone marrow was significantly increased 4 hours after pemetrexed administration. Six weeks after the start of treatment 5 patients had partial response, 4 stable disease and 2 progressive disease. Median TTP was 4.2 months (range 3.0-7.4 months); median OS was 13.0 months (range 5.1-30.8 months). Changes in ¹⁸F-FLT uptake were not predictive for tumor response, TTP or OS.
Measuring TS-inhibition in a clinical setting 4 hours after pemetrexed revealed a non-systematic change in ¹⁸F-FLT uptake within the tumor. No significant association with tumor response, TTP or OS was observed.
培美曲塞是胸苷酸合成酶（TS）抑制剂，对非小细胞肺癌（NSCLC）有效。3'-脱氧-3'-[¹⁸F]氟胸苷（¹⁸F-FLT），一种增殖标志物，可能可以识别肿瘤特异性 TS 抑制。本研究旨在探讨培美曲塞诱导的 TS 抑制对转移性 NSCLC 患者培美曲塞给药后 4 小时¹⁸F-FLT 摄取的影响。
14 名 NSCLC 患者在基线和培美曲塞首次给药后 4 小时进行动态¹⁸F-FLT 正电子发射断层扫描（PET）扫描。使用最大像素的 41%、50%和 70%阈值定义感兴趣的体积。进行了动力学分析和简化测量。在培美曲塞给药后 1、2、4 和 6 小时测量血浆脱氧尿苷作为 TS 抑制的系统指标。使用实体瘤反应评估标准（RECIST）、进展时间（TTP）和总生存期（OS）确定肿瘤反应。
11 名患者在基线和培美曲塞后 4 小时有可评估的¹⁸F-FLT PET 扫描。两名患者在培美曲塞后¹⁸F-FLT 摄取增加了 35%和 31%，而另外两名患者摄取减少了 31%。在其余七名患者中，¹⁸F-FLT 摄取在测试-再测试边界之外没有变化。所有患者在培美曲塞给药后脱氧尿苷水平升高，表明培美曲塞诱导的 TS 抑制。培美曲塞给药后 4 小时骨髓中¹⁸F-FLT 摄取明显增加。治疗开始后 6 周，5 名患者部分缓解，4 名患者病情稳定，2 名患者病情进展。中位 TTP 为 4.2 个月（范围 3.0-7.4 个月）；中位 OS 为 13.0 个月（范围 5.1-30.8 个月）。¹⁸F-FLT 摄取的变化与肿瘤反应、TTP 或 OS 无关。
在培美曲塞给药后 4 小时测量 TS 抑制在临床环境中显示肿瘤内¹⁸F-FLT 摄取的非系统性变化。未观察到与肿瘤反应、TTP 或 OS 有显著相关性。
