Publication Date

Fall 2010

Document Type

Project Summary

Degree Name

Master of Science

Department

Analytical Chemistry

First Advisor

Walter Henne, Jr., Ph.D.

Second Advisor

Stephen Kent, M.B.A.

Third Advisor

Patty Fu-Giles, Ph.D.

Abstract

The folate receptor has achieved great importance for use in targeted drug delivery and in vitro and in vivo diagnostic assays. The folate receptor (FR) is over-expressed on several cancer cell types and activated macrophages, but exists in relatively low abundance on the surface of non-cancerous tissue and non inflammatory cells. This unique attribute is the hallmark of folate-targeted methodologies allowing the diagnostic agent and/or drug to be ferried to the specific disease sites while preventing “off target” effects in normal tissues. Protein toxins, chemotherapeutic agents, radioimaging agents, magnetic resonance imaging (MRI) contrast agents liposomes with entrapped drugs, radiotherapeutic agents, and immunotherapeutic agents are all in current stages of development.

Although several folate-based dyes have been reported, simple and detailed synthetic and purification methods for these conjugates have not been reported. More importantly, several new photostable dyes are now commercially available that have not been tested as folate-based imaging agents. In tandem with the synthesis of these new folate dyes, High Performance Liquid Chromatography (HPLC) purification/analysis by diode array and mass spectrometry will need to be undertaken in order to confirm the identity of the compounds. Thus, our objective is to develop a new folate-based dye and the corresponding HPLC methods for the purification and analysis of this conjugate. Once synthesized, we have several column types of varying lengths, diameters, particle sizes, (we recently acquired ~ 20 “state of the art” columns from industrial sources) and several HPLC’s at our disposal to analyze the compound (via retention time and mass spectrum).

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