[¹⁸F]α/γ-Fluorobenzylamine-folate

Folic acid is a water-soluble B vitamin (1) that is essential for methylation and DNA synthesis. The primary pathway for entry of folate into cells is through the facilitated transporter, which has a low affinity for folate (Michaelis constant (K_m) = 1-5 μM). Some cells in the choroid plexus, kidney, lung, thyroid, spleen, placenta, and thymus also possess a higher affinity (dissociation constant (K_d) = 0.5 nM) receptor that allows folate uptake via receptor-mediated endocytosis. Some human epithelial tumor cells were found to overexpress folate-binding protein (2). More than 90% of human ovarian and endometrial cancers express the high-affinity receptor, which is absent in normal tissues. Breast, colorectal, renal, and lung carcinomas also overexpress the folate receptor but at lower frequencies (20-50%). Activated macrophages, but not resting macrophages, have been also found to have folate receptor (3).

Several folate-based conjugates (¹¹¹In-DTPA-folate, ^99mTc-EC-folate and ^68/67/66Ga-DF-folate) have been studied in tumor imaging (4-7). Bettio et al. (8) reported a synthesis of 18F-labeled folate by a reaction of [¹⁸F]4-fluorobenzylamine (FBA) with the α- and γ-carboxyl groups of folic acid. [18F]α/γ-FBA-folate is being developed as a positron emission tomography (PET) agent for detection of folate receptors in vivo.