Molecular PET Imaging of Cellular Proliferation and HSV-tk Gene Expression:From Bench to Clinic

来源 :BIT Life Sciences' 1st Annual World Cancer Congess-2008( | 被引量 : 0次 | 上传用户:shishaofei
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  Uncontrolled cell division is the defining characteristic of cancer, and many anticancer therapies are aimed directly at inhibiting cell division in tumors.The metabolic process most directly related to cell division is DNA synthesis, andone of the building blocks of DNA is thymidine.Cells form thymidylate (thymidine monophosphate), a necessary precursor of DNA, either by methylation of deoxyuridine monophosphate ("de novo pathway") or by phosphorylation of thymidine (TdR) imported from the extracellular milieu ("salvage pathway").In the salvage pathway thymidine gets phosphorylated by the cellular kinases such as thymidine kinases TK1 and TK2, and TK1 is up-regulated in the S-phase of the cell cycle.Thymidine has been radiolabeled with 11C (t1/2=20 min) for imaging cell proliferation and tumor activity by positron emission tomography (PET).However, in vivo catabolism of thymidine limits it application for this purpose.Many fluorinated analogues of·thymidine such as 2-deoxy-2-fluoro-5-methyl-1-β-D-arabinofuranosyluraeil (FMAU), 2-deoxy-2-fluoro-5-iodo-1-β-D-arabinofuranosyl-uracil (FIAU) and other 5-substituted analogues, and 3-deoxy-3-fluoro-thymidine (FLT) are resistant to catabolic degradation in vivo than thymidine.Radiolabeled FMAU such as 11C and 18Flabeled FMAU were developed by Dr.Alauddin et al.for PET imaging of cellular proliferation.They have also developed 18F-FEAU and 18F-FHBG for PET imaging of HSV-tk gene expression.These radiotracers are currently under investigation in the pre-clinical and clinical applications.11C-FMAU and 18F-FMAU can be used for early detection of tumor, as well as assessment of treatment response of cancer therapy.Similarly, 18F-FEAU and 18F-FHBG can be used for PET imaging of HSV-tk gene expression in gene therapy of cancer.
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