Conti P S, Alauddin M M, Fissekis J R, Schmall B, Watanabe K A
PET Imaging Science Center, University of Southern California, School of Medicine, Los Angeles, CA 90033, USA.
Nucl Med Biol. 1995 Aug;22(6):783-9. doi: 10.1016/0969-8051(95)00017-r.
Rapid in vivo catabolism limits the use of currently available radiotracers used in tumor proliferation studies with PET. This is manifested by the need to develop complex mathematical models to interpret kinetic and metabolite data obtained from imaging studies with agents such as carbon-11 labeled thymidine. A potential carbon-11 labeled radiotracer for cellular proliferation, 2'-fluoro-5-([11C]-methyl)-1-beta-D-arabinofuranosyluracil (FMAU), has been prepared using a previously described method for preparation of [11C]methyl-thymidine where selective alkylation of a pyrimidyl dianion is accomplished with [11C]methyl iodide at the 5-position of the pyrimidine ring. FMAU shares many in vivo characteristics of thymidine, including cellular transport, phosphorylation by mammalian kinase, and incorporation into DNA. Most importantly, in vivo catabolism of FMAU is limited, potentially yielding simplified kinetic models for determination of cellular proliferation with positron emission tomography.
体内快速分解代谢限制了目前正电子发射断层扫描（PET）肿瘤增殖研究中使用的放射性示踪剂的应用。这表现为需要开发复杂的数学模型来解释从使用如碳-11标记胸腺嘧啶核苷等试剂的成像研究中获得的动力学和代谢物数据。一种潜在的用于细胞增殖的碳-11标记放射性示踪剂，2'-氟-5-([11C]-甲基)-1-β-D-阿拉伯呋喃糖基尿嘧啶（FMAU），已使用先前描述的制备[11C]甲基胸腺嘧啶核苷的方法制备，其中嘧啶二价阴离子在嘧啶环的5位用[11C]甲基碘进行选择性烷基化。FMAU具有许多胸腺嘧啶核苷的体内特征，包括细胞转运、被哺乳动物激酶磷酸化以及掺入DNA。最重要的是，FMAU的体内分解代谢受到限制，这可能为通过正电子发射断层扫描确定细胞增殖产生简化的动力学模型。
