Folic Acid, Folate Conjugates and Folate Receptors: Novel Applications in Imaging of Cancer and Inflammation-Related Conditions

Selective delivery of imaging agents to target cells remains a major challenge for molecular imaging and targeted therapy. Folate-based targeting leverages the differential expression of folate receptors (FRs), which are frequently overexpressed in various malignancies and in activated macrophages compared with most normal tissues, to mediate selective cellular uptake. Folate and folate-conjugates offer several advantages for targeted delivery: 1) restricted normal-tissue distribution of FRs, 2) high affinity binding to FRs, and 3) straightforward conjugation chemistry that enables linkage to both therapeutic and imaging moieties. In this narrative review, we summarize recent advances in FR-targeted imaging across multiple modalities (PET, SPECT, MRI, and optical imaging), discuss strategies for probe design and pharmacokinetic optimization, and highlight translational progress from preclinical studies to early clinical applications. We also review emerging applications of folate-mediated delivery for gene therapy and immune modulation, and we identify remaining challenges including probe specificity, background uptake, and clinical validation and outline directions for future research and clinical translation.