Tumor detection using folate receptor-targeted imaging agents

Folate receptors are up-regulated on a variety of human cancers, including cancers of the breast, ovaries, endometrium, lungs, kidneys, colon, brain, and myeloid cells of hematopoietic origin. This over-expression of folate receptors (FR) on cancer tissues can be exploited to target folate-linked imaging and therapeutic agents specifically to FR-expressing tumors, thereby avoiding uptake by most healthy tissues that express few if any FR. Four folate-targeted therapeutic drugs are currently undergoing clinical trials, and several folate-linked chemotherapeutic agents are in late stage preclinical development. However, because not all cancers express FR, and because only FR-expressing cancers respond to FR-targeted therapies, FR-targeted imaging agents have been required to select patients with FR-expressing tumors likely to respond to folate-targeted therapies. This review focuses on recent advances in the use of the vitamin folic acid to target PET agents, γ-emitters, MRI contrast agents and fluorescent dyes to FR⁺ cancers for the purpose of diagnosing and imaging malignant masses with improved specificity and sensitivity.