Adenovirus-mediated gene expression imaging to directly detect sentinel lymph node metastasis of prostate cancer

Abstract

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 prostaterestricted 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.The pathological findings of aggressive prostate cancer have been well documented in a large series of prostatectomy subjects 1,2 . Among the adverse pathologic features, the presence of pelvic lymph node metastasis is the strongest predictor of poor outcome 3 . For instance, the 10-year progression-free survival probabilities were 79% for organ-confined disease, 53% for disease with extraprostatic extension and only 12% for disease with lymph node metastases 1 .

Inhibition of human tumor growth in mice by an oncolytic herpes simplex virus designed to target solely HER-2-positive cells

“…The tumor-selective G207, deleted in ␥ 1 34.5 gene, proved to be very safe when injected intracerebrally in humans in amounts as high as 10 9 pfu, testifying the lack of HSV toxicity even when injected in its target organ. A retargeted HSV could be easily converted into a virus suitable for imaging and metastases detection (38). HSV persists in most of the human population worldwide, and generally causes no-to-mild pathologies; any unwanted virus replication can be blocked by acyclovir.…”

Expression profiling identifies new function of collapsin response mediator protein 4 as a metastasis-suppressor in prostate cancer

“…Among the adverse pathological features, the presence of pelvic lymph node metastasis is the strongest predictor of poor outcome (Burton et al, 2008). Proteomics-based expression profiling has been commonly used to compare and contrast heterogeneous groups of human tumors (Hanash, 2003).…”

Oncolytic Adenovirus ICOVIR-7 in Patients with Advanced and Refractory Solid Tumors

“…Infection of tumor cells results in replication, oncolysis, and subsequent release of the virus progeny. The replicating virus kills infected cancer cells, amplifies and spreads locally, and can also disseminate through the vasculature into metastases (10,11). Moreover, oncolytic replication is an immunogenic phenomenon and antitumor immune responses can be body-wide (2).…”