Imaging Adenovirus-Mediated Gene Transfer

Zinn, Kurt R.; Chaudhuri, Tuhin K.

doi:10.1016/b978-012199504-1/50023-7

Cited by 1 publication

(1 citation statement)

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“…In particular, the use of adenoviral vectors for molecular imaging of cancer offers opportunities to non-invasively gain information regarding tumor location as well as disease-specific information with regards to metabolism, receptor expression or tumor vascularity. 25 Much of the development and clinical application of viral-based vector strategies, however, has been limited by their associated immunogenicity, pathogenicity, and natural tropism. The diagnostic adenovirus, Ad5/3-Id1-SEAP-Id1-mCherry, investigated in this work overcomes many of the challenges commonly associated with viral vectors since it is replication defective and engineered to demonstrate enhanced cancer-specific infectivity.…”

Section: Discussionmentioning

confidence: 99%

A dual-reporter, diagnostic vector for prostate cancer detection and tumor imaging

et al. 2014

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Detection of prostate-specific antigen (PSA) as a screening strategy for prostate cancer is limited by the inability of the PSA test to differentiate between malignant cancer and benign hyperplasia. Here, we report the use of a cancer-specific promoter, inhibition of differentiation-1 (Id1), to drive a dual-reporter system (Ad5/3-Id1-SEAP-Id1-mCherry) designed for detection of prostate cancer using a blood-based reporter SEAP (secreted embryonic alkaline phosphatase) and tumor visualization using a fluorescent reporter protein, mCherry. In human prostate tumors, Id1 levels correlate with increased Gleason grade and disease progression. To evaluate the performance of the dual-reporter system, a prostate cell panel with varying aggressive phenotypes was tested. Following infection with the Ad5/3-Id1-SEAP-Id1-mCherry vector, expression of the SEAP and mCherry reporters was shown to increase with increasing levels of cellular Id1. No correlation was observed between Id1 and PSA. To evaluate in vivo performance, flank tumors were grown in athymic male mice using three prostate cancer cell lines. Following intra-tumoral injection of the vector, tumors formed by cells with high Id1 had the greatest reporter expression. Interestingly, tumors with the lowest levels of Id1 and reporter expression produced the greatest amounts of PSA. These data support the use of Ad5/3-Id1-SEAP-Id1-mCherry as a predictor of prostate cancer malignancy and a strategy for tumor localization.

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Section: Discussionmentioning

confidence: 99%