Nuclear Imaging for Assessment of Prostate Cancer Gene Therapy
Abstract
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. The distribution, expression, and persistence of the prostate specific Ad-PSA-tk in the C4-2 tumor xenograft model will be non-invasively and repeatedly determined in vivo by tracing the 1-123 labeled TK substrates with a SPECT imaging modality. Specific Aim of the first year: To synthesize a radiolabeled TK substrate for TK detection using a small animal gamma detector. In the original plan, we proposed to develop a novel synthetic method of 1-123lVFRU with high specificity. However, after careful literature study, we decide to modify our target molecule labeled with Tc-99m because of its superior physical characteristics (T1/2 = 6h, 140 keV), high specific activity (5 x 105 Ci/mmol), and straightforward production from a Mo-99/Tc-99m generator. Progress and outcome: Although the grant was awarded on March of 2002, due to the hiring process of a postdoctoral fellow the research was started on 10 Sep 2002. Currently, we are in the process of synthesizing 2'-Deoxy-2'fluoro-5-(3-oxoN, N-bis(2-mercaptoethyl)ethylenediaminatoTc-99m technetium(V)-1 (E)-propenyl!uridine, a proposed TK substrate.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2003
- Accession Number
- ADA415953
Entities
People
- Dongfeng Pan
Organizations
- University of Virginia