The objective of this project is to design and evaluate novel folate conjugates targeted to the prostate-specific membrane antigen (PSMA) for prostate cancer imaging. In the Phase I project period, the Specific Aims are: 1. To synthesize novel folate conjugates and determine their affinity for prostate cancer cells in vitro; a series of four folate conjugates will initially be synthesized, labeled with 99mTc and evaluated in cultured prostate cancer cells; 2. To evaluate the tumor localizing properties of the 99mTc-labeled folate conjugates in animal models; biodistribution and pharmacokinetic studies will be carried out in athymic mice carrying human prostate cancer xenografts and the results compared with those obtained with radiolabeled CYT-356, a modified antibody against the PSMA. Successful completion of this project should provide us with the necessary data to determine the merit of further preclinical development and clinical studies of the selected candidate for prostate cancer imaging.

Proposed Commercial Applications

The proposed project could lead to the development of a clinically useful agent for tumor imaging by scintigraphy. This will have a significant impact on the management of prostate cancer patients by providing a rapid and highly sensitive method of tumor diagnosis and staging.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Small Business Innovation Research Grants (SBIR) - Phase I (R43)
Project #
1R43CA081975-01A2
Application #
6333819
Study Section
Special Emphasis Panel (ZCA1-SRRB-E (J2))
Program Officer
Baker, Houston
Project Start
2001-08-14
Project End
2003-08-13
Budget Start
2001-08-14
Budget End
2002-08-13
Support Year
1
Fiscal Year
2001
Total Cost
$171,716
Indirect Cost
Name
Topogen, Inc.
Department
Type
DUNS #
883091076
City
Port Orange
State
FL
Country
United States
Zip Code
32128
Pan, Xing Q; Lee, Robert J (2005) In vivo antitumor activity of folate receptor-targeted liposomal daunorubicin in a murine leukemia model. Anticancer Res 25:343-6
Stevens, Phillip J; Sekido, Masaru; Lee, Robert J (2004) Synthesis and evaluation of a hematoporphyrin derivative in a folate receptor-targeted solid-lipid nanoparticle formulation. Anticancer Res 24:161-5
Stevens, Phillip J; Sekido, Masaru; Lee, Robert J (2004) A folate receptor-targeted lipid nanoparticle formulation for a lipophilic paclitaxel prodrug. Pharm Res 21:2153-7
Chiu, Shih-Jiuan; Ueno, Naoto T; Lee, Robert J (2004) Tumor-targeted gene delivery via anti-HER2 antibody (trastuzumab, Herceptin) conjugated polyethylenimine. J Control Release 97:357-69
Zhao, Xiaobin B; Lee, Robert J (2004) Tumor-selective targeted delivery of genes and antisense oligodeoxyribonucleotides via the folate receptor. Adv Drug Deliv Rev 56:1193-204
Stevens, Phillip J; Lee, Robert J (2003) A folate receptor-targeted emulsion formulation for paclitaxel. Anticancer Res 23:4927-31