The Assessment of gene therapy for bone metastatic lesion of prostate cancer, using Positron Emission Tomography.

为了评估基因治疗前列腺癌的疗效，我们采用正电子发射断层扫描（PET），采用18F-脱氧葡萄糖（[18F]FDG）作为示踪剂，研究了[18F]FDG在肿瘤中的积累情况。首先，我们用Balb/C裸鼠接种人前列腺癌细胞系PC-3，形成PC-3皮下或骨肿瘤。待肿瘤直径为3-5mm（骨肿瘤为4周后）后，将Ad-OC-TK直接注射到肿瘤皮下或骨肿瘤病变处。第1天和第8天的剂量分别为2.5 × 10^9和2.5 × 10^<10>斑块形成单位（PFU），每天给予VAL 21 d。21 d后，小鼠麻醉，通过尾静脉注射[18F] FDG （5.3MBq）。h后处死小鼠，观察[18F] FDG在肿瘤中的积累情况。我们发现，与未接受基因治疗的肿瘤相比，接受基因治疗的肿瘤中[18F] FDG的积累较少。这说明基因治疗后的前列腺癌细胞葡萄糖利用率较低，可以通过观察[18F] FDG的积累来评估基因治疗的治疗效果。此外，我们同样通过尾静脉注射9-[（4-[18F]-氟-3-羟甲基丁基）鸟嘌呤（FHBG）来检测HSV-TK基因的转导作用。与未接受基因治疗的肿瘤相比，经基因治疗的肿瘤中[18F] FHBG的积累较高。该结果提示通过观察[18F] FHBG的积累来评估HSV-TK基因转导作用的可能性。

To evaluate the therapeutic effect of the gene therapy for prostate cancer, we performed Positron Emission Tomography (PET) which employed 18F-deoxyglucose ( [18F]FDG) as a tracer, and investigated accumulation of [18F]FDG in tumor. First, we inoculated PC-3 which is a human prostate cancer cell line with Balb/C nude mouse, we formed a subcutaneous or bone tumor of PC-3. After the tumor diameter was 3-5mm (4 weeks later in bone tumor), Ad-OC-TK was injected directly into the subcutaneous tumor or the bone tumor lesion. The doses used were 2.5 x 10^9 and 2.5 x 10^<10> plaque-forming units (PFU) on Day 1 and 8 and we gave VAL daily for 21 d. After 21 d, mice were anesthetized, and injected via tail vein with [18F] FDG (5.3MBq). After lh, we sacrificed mice, and evaluated accumulation of [18F] FDG in tumor. We demonstrated low accumulation of [18F] FDG in tumor treated by gene therapy compared with no treatment. This result suggested that prostate cancer cells treated by gene therapy were low glucose rate of utilization and it was capable of assessing the therapeutic effect of the gene therapy by observing accumulation of [18F] FDG. Furthermore, we similarly tested the transduction effect of HSV-TK gene by injecting 9-[(4-[18F]-fluoro-3-hydroxymethylbuty1)guanine (FHBG) via tail vein.High accumulation of [18F] FHBG was observed in tumor treated by gene therapy compared with no treatment. This result suggested the possibility of assessing the transduction effect of HSV-TK gene by observing accumulation of [18F] FHBG.