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 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.


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 (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.


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.
Yang
Honghao
H
Department of Medicine, Division of Hematology-Oncology, UCLA School of Medicine, 10833 LeConte Avenue, Los Angeles, CA 90095, USA.
Berger
Frank
F
Tran
Chris
C
Gambhir
Sanjiv S
SS
Sawyers
Charles L
CL
D000212:Acyclovir / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000818:Animals; D004195:Disease Models, Animal; D005434:Flow Cytometry; D005462:Fluorine Radioisotopes / Q000737:chemistry; D005822:Genetic Vectors / Q000235:genetics; D049452:Green Fluorescent Proteins; D006147:Guanine; D018259:Herpesvirus 1, Human / Q000201:enzymology / Q000235:genetics; D006801:Humans; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism; D013937:Thymidine Kinase / Q000235:genetics / Q000378:metabolism; D014055:Tomography, Emission-Computed / Q000379:methods*; D014161:Transduction, Genetic; D014162:Transfection; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D005462:Fluorine Radioisotopes; D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins; C053539:penciclovir; D006147:Guanine; D013937:Thymidine Kinase; D000212:Acyclovir