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 ∼200 μCi 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. 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 (∼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. CONCLUSIONS 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. Prostate 55:39–47, 2003. © 2003 Wiley‐Liss, Inc.