MicroPET imaging of prostate cancer in LNCAP-SR39TK-GFP mouse xenografts

BACKGROUND. 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). METHODS. 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 similar to200 muCi Fluorine-18 labeled penciclovir (F-18-FHBG). PET-images were correlated to tumor size, % injected dose (ID)/g tumor tissue, PSA levels, autoradiography, and histology. RESULTS. 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 (similar to0.2% ID/g). The magnitude of F-18-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 F-18-flurodeoxyglucose (F-18-FDG) gave poor imaging results in LNCaP cells, C-11-acetate gave satisfactory images. CONCLUSIONS. We demonstrated the feasibility of monitoring prostate cancer xenografts in a mouse model using microPET and the HSV1-sr39tk PET reporter gene/F-18-FHBG reporter probe system. Extension of this approach may allow repetitive imaging of tumor metastases. (C) 2003 Wiley-Liss, Inc.