Yang Honghao, Berger Frank, Tran Chris, Gambhir Sanjiv S, Sawyers Charles L
Department of Medicine, Division of Hematology-Oncology, UCLA School of Medicine, 10833 LeConte Avenue, Los Angeles, CA 90095, USA.
Prostate. 2003 Apr 1;55(1):39-47. doi: 10.1002/pros.10208.
The aim of this study was to develop models that allow serial, noninvasive imaging of human prostate cancer cells in immunodeficient mice using a dedicated small animal positron emission tomography scanner (microPET).
LNCaP tumor cells were stably transduced ex-vivo with the mutant herpes simplex virus type 1 thymidine kinase (HSV-sr39tk) PET reporter gene and green fluorescent protein (GFP). The stably transduced LNCaP cells were then enriched via fluorescent cell sorting and implanted into SCID mice. Beginning 2 weeks after tumor cell inoculation, mice were repeatedly scanned by microPET performed 1 hr after tail-vein injection of approximately 200 muCi Fluorine-18 labeled penciclovir ((18)F-FHBG). PET-images were correlated to tumor size, % injected dose (ID)/g tumor tissue, PSA levels, autoradiography, and histology.
Monitoring LNCaP xenografts using microPET and our reporter gene approaches is feasible. MicroPET was capable of detecting subcutaneous tumors as small as 3 mm in diameter (approximately 0.2% ID/g). The magnitude of (18)F-FHBG-uptake in PET-images correlated with the tumor volumes and the serum PSA levels. Other non-HSV1-TK-specific tracers were also studied. While (18)F-flurodeoxyglucose ((18)F-FDG) gave poor imaging results in LNCaP cells, (11)C-acetate gave satisfactory images.
We demonstrated the feasibility of monitoring prostate cancer xenografts in a mouse model using microPET and the HSV1-sr39tk PET reporter gene/(18)F-FHBG reporter probe system. Extension of this approach may allow repetitive imaging of tumor metastases.
本研究的目的是开发能够使用专用小动物正电子发射断层扫描仪（微型PET）对免疫缺陷小鼠体内的人前列腺癌细胞进行连续、无创成像的模型。
LNCaP肿瘤细胞在体外被稳定转导了突变的单纯疱疹病毒1型胸苷激酶（HSV-sr39tk）PET报告基因和绿色荧光蛋白（GFP）。然后通过荧光细胞分选富集稳定转导的LNCaP细胞，并将其植入SCID小鼠体内。在肿瘤细胞接种后2周开始，在尾静脉注射约200μCi氟-18标记喷昔洛韦（（18）F-FHBG）1小时后，用微型PET对小鼠进行重复扫描。PET图像与肿瘤大小、每克肿瘤组织注射剂量百分比（ID）、PSA水平、放射自显影和组织学相关。
使用微型PET和我们的报告基因方法监测LNCaP异种移植瘤是可行的。微型PET能够检测直径小至3mm的皮下肿瘤（约0.2%ID/g）。PET图像中（18）F-FHBG摄取量与肿瘤体积和血清PSA水平相关。还研究了其他非HSV1-TK特异性示踪剂。虽然（18）F-氟脱氧葡萄糖（（18）F-FDG）在LNCaP细胞中的成像效果不佳，但（11）C-醋酸盐给出了满意的图像。
我们证明了使用微型PET和HSV1-sr39tk PET报告基因/（18）F-FHBG报告探针系统在小鼠模型中监测前列腺癌异种移植瘤的可行性。这种方法的扩展可能允许对肿瘤转移进行重复成像。
