Early detection of response to experimental chemotherapeutic Top216 with [18F]FLT and [18F]FDG PET in human ovary cancer xenografts in mice.
Early detection of response to experimental chemotherapeutic Top216 with [18F]FLT and [18F]FDG PET in human ovary cancer xenografts in mice.
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DOI：
10.1371/journal.pone.0012965
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发表时间：
2010-09-24
期刊：
影响因子：
3.7
通讯作者：
Kjær A
中科院分区：
文献类型：
--
作者：
Jensen MM;Erichsen KD;Björkling F;Madsen J;Jensen PB;Højgaard L;Sehested M;Kjær A
3'-脱氧-3'-[18F]氟胸苷 (18F-FLT) 是一种用于评估体内细胞增殖的示踪剂。该研究的目的是使用 18F-FLT 正电子发射断层扫描 (PET) 来研究新型抗癌化合物的治疗反应。为此，我们通过 PET 无创研究了实验性化疗 Top216 的早期抗增殖作用。 在开始 Top216 治疗（0 小时和 48 小时静脉注射 50 mg/kg）后的不同时间点，研究了小鼠人卵巢癌异种移植物 (A2780) 体内 18F-FLT 的摄取。在注射 Top216 (n = 7–10) 或载体 (n = 5–7) 之前进行基线 18F-FLT 扫描，并在治疗 2 和 6 小时以及 1 和 5 天后重复进行。使用 2′-脱氧-2′-[18F]氟-D-葡萄糖 (18F-FDG) 进行了平行研究 (n = 8)。使用小动物 PET/CT 量化示踪剂的摄取。通过肿瘤体积变化以及 Ki67 和 TK1 的基因表达来验证成像结果。与对照组相比，Top216（50 mg/kg 0和48小时）抑制A2780肿瘤的生长（P<0.001）。 Top216治疗后2小时（-52%；P<0.001）、6小时（-49%；P = 0.002）和第1天（-47%；P<0.001）18F-FLT摄取显着下降。第 5 天时，18F-FLT 的摄取量与对照组的摄取量相当。实验期间对照组对 18F-FLT 的摄取没有变化。与基线相比，治疗组中 18F-FDG 的摄取在 6 小时（-21%；P = 0.003）、第 1 天（-29%；P<0.001）和第 5 天（-19%；P = 0.05）时显着下降。注射一次 Top216 后，细胞增殖迅速显着下降，可在 2 小时后通过 18F-FLT 进行评估。肿瘤细胞增殖的早期减少先于肿瘤大小的变化。我们的数据表明，18F-FLT PET 在药物开发中化疗效果的早期非侵入性评估和患者定制治疗方面具有广阔的前景。
3′-deoxy-3′-[18F]fluorothymidine (18F-FLT) is a tracer used to assess cell proliferation in vivo. The aim of the study was to use 18F-FLT positron emission tomography (PET) to study treatment responses to a new anti-cancer compound. To do so, we studied early anti-proliferative effects of the experimental chemotherapy Top216 non-invasively by PET. In vivo uptake of 18F-FLT in human ovary cancer xenografts in mice (A2780) was studied at various time points after Top216 treatment (50 mg/kg i.v. at 0 and 48 hours) was initiated. Baseline 18F-FLT scans were made before either Top216 (n = 7–10) or vehicle (n = 5–7) was injected and repeated after 2 and 6 hours and 1 and 5 days of treatment. A parallel study was made with 2′-deoxy-2′-[18F]fluoro-D-glucose (18F-FDG) (n = 8). Tracer uptake was quantified using small animal PET/CT. Imaging results were validated by tumor volume changes and gene-expression of Ki67 and TK1. Top216 (50 mg/kg 0 and 48 hours) inhibited the growth of the A2780 tumor compared to the control group (P<0.001). 18F-FLT uptake decreased significantly at 2 hours (−52%; P<0.001), 6 hours (−49%; P = 0.002) and Day 1 (−47%; P<0.001) after Top216 treatment. At Day 5 18F-FLT uptake was comparable to uptake in the control group. Uptake of 18F-FLT was unchanged in the control group during the experiment. In the treatment group, uptake of 18F-FDG was significantly decreased at 6 hours (−21%; P = 0.003), Day 1 (−29%; P<0.001) and Day 5 (−19%; P = 0.05) compared to baseline. One injection with Top216 initiated a fast and significant decrease in cell-proliferation assessable by 18F-FLT after 2 hours. The early reductions in tumor cell proliferation preceded changes in tumor size. Our data indicate that 18F-FLT PET is promising for the early non-invasive assessment of chemotherapy effects in both drug development and for tailoring therapy in patients.