Folate receptor targeted imaging agents for the differential diagnosis of cancer from inflammation
Abstract
Over expression of Folate receptors in a variety of tumors led to the discovery of folate receptor based drug delivery and diagnostic agents. FolateScanTM, (EC-20), is a folate derived radiopharmaceutical currently in human clinical trials for the diagnosis and evaluation of folate positive tumors. However, EC-20 has also been used for the diagnosis of inflammatory diseases such as arthritis, atherosclerosis, and ulcerative colitis involving folate receptor beta in activated macrophages. Thus preclinical evaluation of tumor development and response to chemotherapy, is currently limited by the lack of selective noninvasive methodologies suitable for evaluating the tumor in the presence of inflammation. In the research presented herein, we have developed new reduced folate based imaging agents that have shown high specificity and selectivity in animals for folate receptor alpha expressed in cancer and less affinity towards folate receptor beta expressed in macrophages involved in inflammation. Cell studies including human peripheral blood monocytes and in vivo radio and optical imaging studies in different animal models have been performed with the newly synthesized agent to prove their differential selectivity towards cancer over inflammation. Thus, the newly developed cancer specific agent will be a useful addition to the imaging arsenal that can provide additional specificity to prevent false positives during cancer screening and an accurate evaluation for chemotherapy.
Degree
Ph.D.
Advisors
Low, Purdue University.
Subject Area
Biochemistry|Organic chemistry
Off-Campus Purdue Users:
To access this dissertation, please log in to our
proxy server.