Pio Betty S, Park Cecilia K, Pietras Richard, Hsueh Wei-Ann, Satyamurthy Nagichettiar, Pegram Mark D, Czernin Johannes, Phelps Michael E, Silverman Daniel H S
Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA USA.
Mol Imaging Biol. 2006 Jan-Feb;8(1):36-42. doi: 10.1007/s11307-005-0029-9.
The usefulness of 2-deoxy-2-[F-18]fluoro-D-glucose (FDG)-positron emission tomography (PET) in monitoring breast cancer response to chemotherapy has previously been reported. Elevated uptake of FDG by treated tumors can persist however, particularly in the early period after treatment is initiated. 3'-[F-18]Fluoro-3'-deoxythymidine (FLT) has been developed as a marker for cellular proliferation and, in principle, could be a more accurate predictor of the long-term effect of chemotherapy on tumor viability. We examined side-by-side FDG and FLT imaging for monitoring and predicting tumor response to chemotherapy.
Fourteen patients with newly diagnosed primary or metastatic breast cancer, who were about to commence a new pharmacologic treatment regimen, were prospectively studied. Dynamic 3-D PET imaging of uptake into a field of view centered over tumor began immediately after administration of FDG or FLT (150 MBq). After 45 minutes of dynamic acquisition, a clinically standard whole-body PET scan was acquired. Patients were scanned with both tracers on two separate days within one week of each other (1) before beginning treatment, (2) two weeks following the end of the first cycle of the new regimen, and (3) following the final cycle of that regimen, or one year after the initial PET scans, whichever came first. (Median and mean times of early scans were 5.0 and 6.6 weeks after treatment initiation; median and mean times for late scans were 26.0 and 30.6 weeks after treatment initiation.) Scan data were analyzed on both tumor-by-tumor and patient-by-patient bases, and compared to each patient's clinical course.
Mean change in FLT uptake in primary and metastatic tumors after the first course of chemotherapy showed a significant correlation with late (av. interval 5.8 months) changes in CA27.29 tumor marker levels (r = 0.79, P = 0.001). When comparing changes in tracer uptake after one chemotherapy course versus late changes in tumor size as measured by CT scans, FLT was again a good predictor of eventual tumor response (r = 0.74, P = 0.01). Tumor uptake of FLT was near-maximal by 10 minutes after injection. The time frame five to 10 minutes postinjection of FLT produced standardized uptake value (SUV) values highly correlated with SUV values obtained after 45-minute uptake (r = 0.83, P < 0.0001), and changes in these early SUVs after the first course of chemotherapy correlated with late changes in CA27.29 (r = 0.93, P = 0.003).
A 10-minute FLT-PET scan acquired two weeks after the end of the first course of chemotherapy is useful for predicting longer-term efficacy of chemotherapy regimens for women with breast cancer.
先前已有报道称2-脱氧-2-[F-18]氟-D-葡萄糖（FDG）正电子发射断层扫描（PET）在监测乳腺癌化疗反应方面的效用。然而，经治疗的肿瘤对FDG的摄取升高可能会持续存在，尤其是在开始治疗后的早期阶段。3'-[F-18]氟-3'-脱氧胸苷（FLT）已被开发为一种细胞增殖标志物，原则上，它可能是化疗对肿瘤生存能力长期影响的更准确预测指标。我们对FDG和FLT成像进行了对比研究，以监测和预测肿瘤对化疗的反应。
前瞻性研究了14例新诊断的原发性或转移性乳腺癌患者，这些患者即将开始新的药物治疗方案。在给予FDG或FLT（150MBq）后，立即对以肿瘤为中心的视野进行动态三维PET成像。动态采集45分钟后，进行临床标准的全身PET扫描。在一周内的两个不同日期，用两种示踪剂对患者进行扫描：（1）在开始治疗前；（2）新方案第一个周期结束后两周；（3）该方案最后一个周期后，或在首次PET扫描后一年，以先到者为准。（早期扫描的中位时间和平均时间分别为治疗开始后5.0周和6.6周；晚期扫描的中位时间和平均时间分别为治疗开始后26.0周和30.6周。）对每个肿瘤和每个患者的扫描数据进行分析，并与每个患者的临床病程进行比较。
第一个化疗疗程后，原发性和转移性肿瘤中FLT摄取的平均变化与CA27.29肿瘤标志物水平的晚期（平均间隔5.8个月）变化显著相关（r = 0.79，P = 0.001）。当比较一个化疗疗程后示踪剂摄取的变化与CT扫描测量的肿瘤大小的晚期变化时，FLT再次是最终肿瘤反应的良好预测指标（r = 0.7
