Non-invasive bioluminescent detection of prostate cancer growth and metastasis in a bigenic transgenic mouse model
ABSTRACT We previously established a bioluminescent transgenic mouse model, sPSA-Luc, with luciferase gene expression restricted to the prostate under the control of the supra prostate-specific antigen (sPSA) promoter. We now assess the feasibility of generating bigenic mice, TRAMP-Luc, with the sPSA-Luc as the founder strain crossbred with TRAMP (transgenic adenocarcinoma mouse prostate) mice, to evaluate non-invasively the metastatic potential of prostate tumors.
TRAMP-Luc mice were obtained as [C57BL/6 TRAMP x FVB sPSA-Luc] F1 offspring. Tumor development in 10 TRAMP-Luc males was followed by bioluminescence imaging from 8 to 24 weeks of age. Immunohistochemical (IHC) staining for T antigen (Tg), androgen receptor (AR), luciferase and/or pathological analysis verified the tumor distribution in the imaged tissues including prostate gland, lymph node and bone.
Group I animals that presented with no grossly visible tumors showed prostate-confined bioluminescence with slightly increased signal intensity with age. Group II animals that developed large tumors displayed a widely distributed and biphasic bioluminescence pattern. The peak was reached between 10 and 14 weeks of age, then markedly decreased or even disappeared beyond week 16, except for one mouse that showed an increased bioluminescence signal at the jaw bone and hind limbs at week 22. These tumors were shown by IHC to contain Tg but lost AR and luciferase beyond week 16 in poorly differentiated prostate tumors.
A direct correlation between bioluminescence emission and AR expression was found in TRAMP-Luc tumor progression model. This model allows non-invasive imaging of prostate cancer metastases to bone and soft tissues.
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ABSTRACT: Prostate cancer remains an important and growing health problem. Advances in imaging of prostate cancer may help to achieve earlier and more accurate diagnosis and treatment. We review the various strategies using reporter genes for molecular imaging of prostate cancer. These approaches are emerging as valuable tools for monitoring gene expression in laboratory animals and humans. Further development of more sensitive and selective reporters, combined with improvements in detection technology, will consolidate the position of reporter gene imaging as a versatile method for understanding of intracellular biological processes and the underlying molecular basis of prostate cancer, as well as potentially establishing a future role in the clinical management of patients afflicted with this disease.Seminars in Nuclear Medicine 02/2008; 38(1):9-19. DOI:10.1053/j.semnuclmed.2007.09.002 · 3.13 Impact Factor
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ABSTRACT: Bioluminescence imaging (BLI) is a facile method for studying androgen receptor (AR) signaling during tumor progression in xenografts and genetic models of prostate cancer in mice. This chapter summarizes work where BLI and positron emission tomography coupled with CT were used to analyze AR-mediated transcriptional activity using gene expression-based imaging approaches.Androgen Action in Prostate Cancer, 12/2008: pages 91-120;