PET Imaging of Proliferation with Pyrimidines
PET Imaging of Proliferation with Pyrimidines
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DOI：
10.2967/jnumed.112.112201
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发表时间：
2013-06-01
影响因子：
9.3
通讯作者：
Shields, Anthony F.
中科院分区：
文献类型：
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作者：
Tehrani, Omid S.;Shields, Anthony F.
正在开发几种新的示踪剂，用于PET评估癌症中改变的途径，包括能量使用，细胞信号传导，运输和增殖。由于增殖增加是许多癌症的标志，因此已经测试了几种示踪剂来跟踪DNA合成途径。胸苷，它被掺入DNA而不是RNA，已被用于实验室研究，以衡量肿瘤的生长。因为用C-11标记的胸苷经历快速的生物降解并且具有短的物理半衰期，所以用F-18标记的示踪剂在PET成像中是优选的。一种这样的示踪剂是F-18标记的3 '-脱氧-3'-氟胸苷（F-18-FLT）。F-18-FLT被胸苷激酶1磷酸化后捕获，胸苷激酶1在复制细胞中的表达增加。对乳腺、肺和脑肿瘤的几项研究表明，F-18-FLT的保留与肿瘤增殖相关。虽然F-18-FLT已用于几种肿瘤类型的成像和分期，但标准化摄取值通常低于F-18-FDG。F-18-FLT可用于身体的许多区域成像，但在肝脏、骨髓和肾脏系统中的背景摄取较高，限制了在这些器官中的使用。F-18-FLT PET成像主要用于评估治疗反应。在接受细胞毒性药物、靶向药物和放疗治疗的几种肿瘤类型中，F-18-FLT滞留在数天至数周内迅速下降。进一步的工作正在进行中，以验证这种方法，并确定其在新药开发和标准治疗方法的临床评价中的效用。
Several new tracers are being developed for use with PET to assess pathways that are altered in cancers, including energy use, cellular signaling, transport, and proliferation. Because increased proliferation is a hallmark of many cancers, several tracers have been tested to track the DNA synthesis pathway. Thymidine, which is incorporated into DNA but not RNA, has been used in laboratory studies to measure tumor growth. Because thymidine labeled with C-11 undergoes rapid biologic degradation and has a short physical half-life, tracers labeled with F-18 have been preferred in PET imaging. One such tracer is F-18-labeled 3 '-deoxy-3 '-fluorothymidine (F-18-FLT). F-18-FLT is trapped after phosphorylation by thymidine kinase 1, whose expression is increased in replicating cells. Several studies on breast, lung, and brain tumors have demonstrated that retention of F-18-FLT correlated with tumor proliferation. Although F-18-FLT has been used to image and stage several tumor types, the standardized uptake value is generally lower than that obtained with F-18-FDG. F-18-FLT can be used to image many areas of the body, but background uptake is high in the liver, marrow, and renal system, limiting use in these organs. F-18-FLT PET imaging has primarily been studied in the assessment of treatment response. Rapid declines in F-18-FLT retention within days to weeks have been demonstrated in several tumor types treated with cytotoxic drugs, targeted agents, and radiotherapy. Further work is ongoing to validate this approach and determine its utility in the development of new drugs and in the clinical evaluation of standard treatment approaches.