Nuclear Imaging for Assessment of Prostate Cancer Gene Therapy
Abstract
Background: Combination of the cytotoxic viral thymidine kinase (tk) and the prodrug, acyclovir (ACV) has been reported to inhibit the growth of the C4-2 tumor, a subline of LNCaP. However, it remains unsolved to non-invasively detect the in vivo distribution, expression and persistence of the toxic gene as well as to evaluate the therapeutic effect. In this project, we will develop a nuclear gene imaging approach to assist the cytotoxic gene therapy study for prostate cancer. Objective/Hypothesis: The distribution, expression, and persistence of the prostate specific Ad-PSA-tk in the C4-2 tumor xenograft model will be noninvasively and repeatedly determined in vivo by tracing the radiolabeled TK substrates with a SPECT imaging modality. Specific Aim of the first year: To synthesize a radiolabeled TK substrate, 2 -Deoxy-2 fluoro-5-{3-oxo[N,N-bis(2- mercaptoethyl)ethylenediaminato][Tc-99m] technetium(V)-1(E)-propenyl}uridine, for TK detection using a small animal gamma detector. Progress and outcome: In last report of 2003 which covers from September of 2002 to March of 2003, we reported our efforts to synthesize fragments A and B. In this report we successfully linked the radiometal chelator with fluorothymidine. We will characterize the structure of the final tracer and test the pharmacokinetics and pharmacodynamics of the tracer in next research year. Also, the Adenoviral vectors with reporter genes of tk and luciferase were constructed. The luciferase gene expression in live mouse model was non-invasively imaged and the result was posted in 2003 Annual Meeting of ASGT (American Society of Gene Therapy).
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2006
- Accession Number
- ADA459865
Entities
People
- Dongfeng Pan
Organizations
- University of Virginia