Folate based radiopharmaceuticals for imaging and therapy of cancer and inflammation.

Frequent overexpression of the folate receptor (FR) on a variety of tumor types and on activated macrophages makes this receptor an interesting target for both imaging and therapy of cancer and inflammation. The FR is a glycosylphophatidylinositol-anchored protein that binds the vitamin folic acid with high affinity and internalizes it via endocytosis. In normal tissues and organs, FR-expression is restricted to only a few sites where it is confined to the luminal surface of polarized epithelia and hence does not have access to intra-venously administered folic acid conjugates. Thus, using folic acid as a molecular "Trojan horse" to deliver attached probes to the diseased tissue has emerged as a powerful strategy. A variety of folic acid radioconjugates for potential application in nuclear medicine have been developed and (pre)clinically evaluated during the last two decades. Herein we report on folate receptor targeted tracer design and in vitro/in vivo investigations using folic acid -targeted radioconjugates suitable for SPECT and PET imaging as well as for potential therapeutic purposes.