The accurate assessment of nodal involvement in prostate cancer is crucial to planning treatment, yet there is a shortage of noninvasive imaging techniques capable of visualizing nodal lesions directly. This study demonstrates the feasibility of using recombinant human adenoviral vectors to detect nodal metastases in a human prostate cancer model. This was achieved by the prostate-restricted expression of optical and positron emission tomography (PET) imaging reporter genes by the viral vector coupled with the innate lymphotropic properties of adenovirus. We show that peritumoral administration of these vectors results in the direct detection of reporter gene expression in metastatic lesions within sentinel lymph nodes. Notably, this approach parallels the current lymphoscintigraphy method but enables the direct PET visualization of sentinel lymph node metastases, eliminating the need for invasive lymphadenectomy. These findings may lead to more effective diagnostic and therapeutic strategies for individuals with advanced-stage prostate cancer.
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We thank M.E. Black (Washington State University) for antibody to HSV-tk. We appreciate the discussions provided by E. Brakenhielm, A. Cochran and J. DeKernion. This work is supported by the US National Cancer Institute Specialized Programs of Research Excellence (SPORE) program grants P50 CA092131 and RO1 CA101904-01, US Department of Defense grant DAMD17-03-1-0095 and the Prostate Cancer Foundation (to L.W.) and by US National Cancer Institute grant 2U24 CA092865 (to A.F.C.). J.B.B. is supported by UCLA Research Training in Pharmacological Sciences grant T32-GM008652 and US Department of Defense grant CDMRP 07-1-0064. We are indebted to the technical support provided by W. Ladno, J. Edwards and A. Luu of Crump Institute of Molecular Imaging.
D.S. is a consultant with Siemens Preclinical Solutions and a stock owner of Molecular Imaging Products.
Supplementary Text and Figures
Supplementary Figs. 1 and 2 (PDF 1433 kb)
Supplementary Video 1
Progression of 18FLT PET/CT detectable lymph node metastasis following resection of primary tumor, CWR22Rv-1. (MOV 17034 kb)
Supplementary Video 2
18FHBG PET/CT video of AdTSTA-sr39tk mediated visualization of sentinel lymph node metastasis. (MOV 3621 kb)
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Burton, J., Johnson, M., Sato, M. et al. Adenovirus-mediated gene expression imaging to directly detect sentinel lymph node metastasis of prostate cancer. Nat Med 14, 882–888 (2008). https://doi.org/10.1038/nm.1727
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