Folate -targeted imaging agents

Michael David Kennedy, Purdue University

Abstract

In this thesis, folate conjugates with imaging agents are studied as tumor tissue diagnostics. The last chapter of this thesis is a study using these imaging technologies to characterize the uptake of folate conjugates into the choroid plexus of the brain. In order to determine whether folate targeting of a fluorophore could give enhanced fluorescence of tumor tissues, a folate conjugate of fluorescein was developed and tested in mouse tumor models. The results from these studies show greatly increased fluorescent contrast between tumor and nontumor tissues in peritoneal, metastatic, and subcutaneous tumor models. A conjugate of folate with a near-infrared dye was also tested and shown to allow imaging of tumor tissue buried under non-tumor tissue. A technetium chelator, mercaptoacetyltriglycine, conjugated to folate was tested as a radioimaging agent. The conjugate had high stability, good cell uptake into a folate receptor expressing cell line, and in vivo uptake into tumor tissue that was competed with free folate. Magnetic resonance imaging (MRI) using a folate-DTPA conjugate in tumor bearing mice showed increased contrast in tumors compared to nontumor tissue. A positron emission tomography, folate-DOTA, was also developed and tested in vitro and in vivo. The results showed competable uptake in cells and in tumors. The uptake of folate-conjugates into the choroid plexus of the brain was also explored. We found that folate receptors of the choroid plexus are able to bind to small molecular weight folate conjugates; however, large molecular weight conjugates of folate with proteins are not accessible to folate receptors on choroid plexus cells.

Degree

Ph.D.

Advisors

Low, Purdue University.

Subject Area

Oncology|Radiology

COinS