Nuclear Imaging for Assessment of Prostate Cancer Gene Therapy
Annual rept. 12 Mar 2002-11 Mar 2003
VIRGINIA UNIV CHARLOTTESVILLE
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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 T12 6h, 140 keV, high specific activity 5 x 105 Cimmol, and straightforward production from a Mo-99Tc-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-2fluoro-5-3-oxoN, N-bis2-mercaptoethylethylenediaminatoTc-99m technetiumV-1 E-propenyluridine, a proposed TK substrate.
- Medicine and Medical Research