Synthesis and Biological Evaluation of EC20: A New Folate-Derived, 99mTc-Based Radiopharmaceutical
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- 1 November 2002
- journal article
- research article
- Published by American Chemical Society (ACS) in Bioconjugate Chemistry
- Vol. 13 (6) , 1200-1210
- https://doi.org/10.1021/bc0200430
Abstract
A new peptide derivative of folic acid was designed to efficiently coordinate 99mTc. This new chelate, referred to as EC20, was found to bind cultured folate receptor (FR)-positive tumor cells in both a time- and concentration-dependent manner with very high affinity (KD ∼ 3 nM). Using an in vitro relative affinity assay, EC20 was also found to effectively compete with 3H-folic acid for cell binding when presented either alone or as a formulated metal chelate. Following intravenous injection into Balb/c mice, 99mTc-EC20 was rapidly removed from circulation (plasma t1/2 ∼ 4 min) and excreted into the urine in a nonmetabolized form. Data from γ scintigraphic and quantitative biodistribution studies performed in M109 tumor-bearing Balb/c mice confirmed that 99mTc-EC20 predominantly accumulates in FR-positive tumor and kidney tissues. These results suggest that 99mTc-EC20 may be clinically useful as a noninvasive radiodiagnostic imaging agent for the detection of FR-positive human cancers.Keywords
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