Recent advances in PET imaging of folate receptor positive diseases

Folate receptor (FR) is overexpressed on a variety of cancers (FR-α) and on activated macrophages (FR-β), with limited or no expression on most normal cells. This restricted distribution of FR to malignant and inflamed cell types has enabled the use of folic acid to deliver attached drugs selectively to associated pathologies, thereby avoiding unwanted the uptake and derived collateral toxicity to normal tissues. Folate-based radiotracers have also been found to serve as versatile agents for the diagnosis, staging, and prediction of response to therapy of patients with FR-expressing cancers and inflammatory/autoimmune diseases. In this review, we summarize the properties of ¹⁸F-labeled folate conjugates that have undergone preclinical evaluation during the past decade. The advantages and disadvantages of these folate-targeted PET agents, as well as the pros and cons of several emerging ¹⁸F-folate PET imaging agents, are discussed.