Development of Imaging and Quantitation of Gene Induction and Expression using Nuclear Medicine Technique

为了用正电子发射断层扫描评价正电子发射体标记的放射性药物在脑肿瘤中的摄取，对示踪剂摄取进行了体外评价。首先，我们在星形细胞瘤细胞系SW1088和U-118 MG中进行了[F-18]脱氧葡萄糖(FDG)摄取实验。这些细胞系对FDG的摄取以细胞数量依赖的方式增加。当细胞数为15×104和21×104时，这些细胞对FDG的摄取率分别为26.7%和32.5%。其次使用氨基酸示踪剂[F-18]氟甲基酪氨酸(FMT)。当细胞数为7.5×104和10.8×104时，FMT的摄取率分别为7.7%和10.8%。第三，我们使用了[C-11]胆碱：磷脂酰胆碱的前体。U-118 MG在细胞数为17×10~(-4)时的摄取率为11.2%，且摄取具有温度依赖性。结果表明，这些细胞系积累了正电子发射体标记的葡萄糖、氨基酸和胆碱等生物标志物，并可以进行定量评估。虽然FDG是诊断恶性肿瘤的有代表性的示踪剂，但它的摄取并不是恶性肿瘤所特有的。FMT和[C-11]胆碱也可用于细胞增殖和肿瘤恶性程度的诊断。根据这些结果，可以通过摄取FDG作为葡萄糖代谢的示踪剂，以及FAMT和[C-11]胆碱作为示踪剂来评估基因治疗的效果。利用核医学技术可以对基因的诱导和表达进行评估。

To evaluate the uptake of radiopharmaceuticals labeled with positron emitter in the brain tumor using positron emission tomography, in vitro evaluation of tracer uptake was examined. Firstly we performed [F-18] fluorodeoxyglucose (FDG) uptake in astrocytoma cell lines SW1088 and U-118MG. Uptake of FDG in these cell lines increased in a cell number dependent manner. The uptake of FDG in these cell lines was 26.7% and 32.5% at cell number of 15×10^4 and 21×10^4, respectively. Secondly amino-acid tracer [F-18] fluoromethyl tyrosine (FMT) was used. The uptake of FMT was 7.7% and 10.8% at cell number of 7.5×10^4 and 10.8×10^4, respectively. Tertiary we used [C-11] choline : precursor of phosphatidyl choline. The uptake in U-118MG was 11.2% at cell number of 17×10^4 and the uptake was temperature dependent. The results indicated that these cell lines accumulate positron emitter labeled biomarkers of glucose, amino acid and choline, and quantitative evaluation was possible.Clinical evaluation of these tracers was performed in cases with brain tumor. Although FDG is a representative tracer for the diagnosis of malignant tumors, its uptake is not specific for the malignant tumor. FMT and [C-11] choline may be also useful for the diagnosis in terms of cell proliferation and tumor malignancy.Based on these results the effect of gene therapy could be evaluated by the uptake of FDG as a tracer for glucose metabolism and also FAMT and [C-11] choline as tracers to correlate activity of tumor. Gene induction and evaluation of its expression could be evaluable by means of nuclear medicine technique.