Accession Number : ADA472763


Title :   Nuclear Imaging for Assessment of Prostate Cancer Gene Therapy


Descriptive Note : Final rept. 12 Mar 2002-11 Feb 2007


Corporate Author : VIRGINIA UNIV CHARLOTTESVILLE


Personal Author(s) : Pan, Dongfeng


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a472763.pdf


Report Date : Mar 2007


Pagination or Media Count : 14


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 non-invasively 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'fiuoro-5-(oxo[N,N-bis(2- mercaptoethyl)ethylenediaminato] [Tc-99m] technetium(V)-1 (E)-propenyl}urid ine 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).


Descriptors :   *PHARMACOKINETICS , *PROSTATE CANCER , TOXICITY , SUBSTRATES , GAMMA RAYS , THERAPY , VIRUSES , PHARMACOLOGY , ANATOMICAL MODELS , DISEASE VECTORS , GENE THERAPY , THYMIDINES , LUCIFERASE , PHOSPHORUS TRANSFERASES , NUCLEAR PHYSICS , ADENOVIRUSES , IN VIVO ANALYSIS , MICE , GENES , CYTOTOXINS , HYPOTHESES


Subject Categories : Anatomy and Physiology
      Medicine and Medical Research
      Pharmacology


Distribution Statement : APPROVED FOR PUBLIC RELEASE