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- W2409009168 abstract "Folic acid (folate) 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 (Km) = 1–5 μM). Some cells in the choroid plexus, kidney, lung, thyroid, spleen, placenta, and thymus also possess a higher-affinity receptor (dissociation constant (Kd) = 0.5 nM) that allows folate uptake via receptor-mediated endocytosis. Some human epithelial tumor cells have been found to overexpress folate receptors (2). More than 90% of human ovarian and endometrial cancers express the high-affinity folate receptor, which is absent in the corresponding normal tissues. Breast, colorectal, renal, and lung carcinomas also overexpress the high-affinity folate receptor but at lower frequencies (20%–50%). Activated macrophages, but not resting macrophages, have also been found to have the high-affinity folate receptor (3).Several folate-based conjugates (111In-DTPA-folate, 99mTc-EC-folate, and [18F]FBA-folate) have been studied in tumor imaging (4-8). Deferoxamine (DF), a chelating agent, was conjugated to folic acid to form a mixture of two isomers, DF-α-folate and DF-γ-folate. Only the DF-γ-folate isomer was able to displace [3H]folic acid from its receptors, with a 50% inhibition concentration similar to that of folic acid (2.5 nM versus 2.4 nM) (9). Fani et al. (10) prepared a γ-folate conjugate with tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA) and 1,2-diaminoethane as a spacer to form P3026 , which was labeled with 68Ga for positron emission tomography (PET) imaging of folate receptors in tumors. To further the quest for a 68Ga-folate conjugate for clinical application, 5,8-dideazfolic acid was conjugated to 1,4,7-triazacyclononane,1-glutaric acid-4,7-acetic acid (NODAGA) via 1,2-diaminoethane as a linker between the NODAGA and 5,8-dideazfolic acid (P3238) (11). 68Ga-P3238 was evaluated as a PET agent for imaging folate receptor expression in a mouse tumor model. 68Ga-P3238 exhibited a lower tumor/blood ratio than 68Ga-P3246 (68Ga-NODAGA-folate) but a higher ratio than 68Ga-3026 in the same tumor model." @default.
- W2409009168 created "2016-06-24" @default.
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- W2409009168 date "2012-09-20" @default.
- W2409009168 modified "2023-09-27" @default.
- W2409009168 title "68Ga-1,4,7-Triazacyclononane,1-glutaric acid-4,7-acetic acid-1,2-diaminoethane-γ-5,8-dideazfolic acid (P3238)" @default.
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