99mTc-1,4,7-Tris(carboxymethyl)-10-(4-aminoethyl)-1,4,7,10-tetraazacyclododecane-Folate

Excerpt

Folic acid is a water-soluble B vitamin (1). It is essential for methylation and DNA synthesis. The primary pathway for entry of folate into cells is through a facilitated transporter, which has a low affinity for folate (K_m, 1–5 μM). Some cells in the choroid plexus, kidney, lung, thyroid, spleen, placenta, and thymus also possess a receptor with higher affinity (K_d, 0.5 nM), which allows folate uptake via receptor-mediated endocytosis. Some human epithelial tumor cells were found to overexpress folate receptors (2). More than 90% of human ovarian and endometrial cancers express the high-affinity receptor, which is absent in the normal tissues. Breast, colorectal, renal, and lung carcinomas also overexpressed the high-affinity folate receptor but to a lesser frequency (20%–50%). Several ^99mTc-based folate conjugates have been developed for single-photon emission computed tomography (SPECT) imaging of folate receptor expression in tumors such as ^99mTc-ethylenedicysteine-folate, ^99mTc-HYNIC-Folate, and ^99mTc-DTPA-Folate (3). Mishra et al. (4) prepared ^99mTc-1,4,7-tris(carboxymethyl)-10-(4-aminoethyl)-1,4,7,10-tetraazacyclododecane-folate (^99mTc-DO3A-EA-Folate) as a new ^99mTc-based folate conjugate for SPECT imaging studies.