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MicroPET imaging of prostate cancer in LNCAP‐SR39TK‐GFP mouse xenografts
Author(s) -
Yang Honghao,
Berger Frank,
Tran Chris,
Gambhir Sanjiv S.,
Sawyers Charles L.
Publication year - 2003
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.10208
Subject(s) - lncap , reporter gene , prostate cancer , thymidine kinase , genetic enhancement , green fluorescent protein , cancer research , nuclear medicine , medicine , pathology , microbiology and biotechnology , cancer , chemistry , biology , herpes simplex virus , gene expression , gene , immunology , virus , biochemistry
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.