Early detection of tumor response to chemotherapy by 3′-deoxy-3′-[18 F]fluorothymidine positron emission tomography:: The effect of cisplatin on a fibrosarcoma tumor model in vivo
Early detection of tumor response to chemotherapy by 3′-deoxy-3′-[18 F]fluorothymidine positron emission tomography:: The effect of cisplatin on a fibrosarcoma tumor model in vivo
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DOI：
10.1158/0008-5472.can-04-4008
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发表时间：
2005-05-15
期刊：
影响因子：
11.2
通讯作者：
Aboagye, EO
中科院分区：
文献类型：
--
作者：
Leyton, J;Latigo, JR;Aboagye, EO
我们评估了[F-18]氟胸苷正电子发射断层扫描[F-18]FLT-PET）测量放射诱导纤维肉瘤1（RIF-1）荷瘤小鼠顺铂治疗诱导的早期细胞抑制和细胞毒性的潜力。通过[F-18]FLT-PET可分别在24和48小时检测到顺铂介导的肿瘤细胞生长停滞和肿瘤收缩诱导。在24和48小时，与对照组（1.02 +/- 0.12）相比，[F-18]FLT在60分钟的标准化摄取（放射性示踪剂注射后60分钟的肿瘤/肝脏放射性比; NUV 60）分别为0.76 +/-0.08（P = 0.03）和0.51 +/- 0.08（P = 0.03）。尽管肿瘤大小无变化，但24小时时[F-18]FLT摄取的减少与化学计量学评估的细胞增殖减少相关（增殖细胞核抗原标记指数LPCNA从14.0 +/- 2.0%降至6.2 +/- 1.0%; P = 0.001）。细胞周期分析显示顺铂处理后细胞出现G（1）-S和G（2）-M期阻滞。对于肿瘤细胞增殖的定量测量，发现[F-18]FLT-PET上级[F-18]氟脱氧葡萄糖-PET（NUV 60与LIPPCNA：分别为r = 0.89，P = 0.001和r = 0.55，P = 0.06）。在生化水平上，我们发现[F-18]FLT和[F-18]氟脱氧葡萄糖摄取的变化是由于胸苷激酶1蛋白、己糖激酶和ATP水平的变化。这项工作支持进一步开发[F-18]FLT-PET作为体内药物诱导细胞增殖变化的早期定量成像的通用药效学读数。
We have assessed the potential of [F-18]fluorothymidinepositron emission tomography [F-18]FLT-PET) to measure early cytostasis and cytotoxicity induced by cisplatin treatment of radiation-induced fibrosarcoma 1 (RIF-1) tumor-bearing mice. Cisplatin-mediated arrest of tumor cell growth and induction of tumor shrinkage at 24 and 48 hours, respectively, were detectable by [F-18]FLT-PET. At 24 and 48 hours, the normalized uptake at 60 minutes (tumor/liver radioactivity ratio at 60 minutes after radiotracer injection; NUV60) for [F-18]FLT was 0.76 +/- 0.08 (P = 0.03) and 0.51 +/- 0.08 (P = 0.03), respectively, compared with controls (1.02 +/- 0.12). The decrease in [F-18]FLT uptake at 24 hours was associated with a decrease in cell proliferation assessed immunohistochemically (a decrease in proliferating cell nuclear antigen labeling index, LIPCNA, from 14.0 +/- 2.0% to 6.2 +/- 1.0%; P = 0.001), despite the lack of a change in tumor size. There were G(1)-S and G(2)-M phase arrests after cisplatin treatment, as determined by cell cycle analysis. For the quantitative measurement of tumor cell proliferation, [F-18]FLT-PET was found to be superior to [F-18]fluorodeoxglucose-PET (NUV60 versus LIPCNA: r = 0.89, P = 0.001 and r = 0.55, P = 0.06, respectively). At the biochemical level, we found that the changes in [F-18]FLT and [F-18]fluorodeoxglucose uptake were due to changes in levels of thymidine kinase 1 protein, hexokinase, and ATP. This work supports the further development of [F-18]FLT-PET as a generic pharmacodynamic readout for early quantitative imaging of drug-induced changes in cell proliferation in vivo.