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DMTHF-Tc
Folate targeting is an imaging and drug delivery method where the folate receptor (FR), being upregulated on malignant and inflamed cell types, is targeted to reduce drug toxicity as well as to visualize and/or to quantify the amount of disease in cancerous and inflamed tissue.〔 In normal tissues, the FR shows limited distribution. However, in cancer cells, FR-α shows upregulation, while FR-β expression is increased in inflamed tissues on activated macrophages. Because the receptor has these two isoforms that are only 76% homologous, the isoforms can be selectively bound in different types of diseased tissue for folate targeting.
The modified folate 5N,10N-dimethyl tetrahydrofolic acid (DMTHF) shows selectivity for FR-α over FR-β.〔 A 99mTc-chelate conjugate of DMTHF, developed by the Philip Low lab at Purdue University, can be used for selective imaging of cancerous tissues where FR-α is overexpressed.
==Synthesis==
DMTHF is derived from Technetium (99mTc) etarfolatide (EC20), another 99mTc-based folate-linked chelator produced by Endocyte for folate-targeted imaging. 99mTc-EC20 is used to image sites of inflammation via FR-β. With the addition of two methyl groups, the dimethylated derivative shows selectivity for the α-isoform over the β-isoform of the FR.〔
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