Synthesis and biological evaluation of EC20: a new folate-derived, (99m)Tc-based radiopharmaceutical.
A new peptide derivative of folic acid was designed to efficiently coordinate (99m)Tc. 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 (K(D) approximately 3 nM). Using an in vitro relative affinity assay, EC20 was also found to effectively compete with (3)H-folic acid for cell binding when presented either alone or as a formulated metal chelate. Following intravenous injection into Balb/c mice, (99m)Tc-EC20 was rapidly removed from circulation (plasma t(1/2) approximately 4 min) and excreted into the urine in a nonmetabolized form. Data from gamma scintigraphic and quantitative biodistribution studies performed in M109 tumor-bearing Balb/c mice confirmed that (99m)Tc-EC20 predominantly accumulates in FR-positive tumor and kidney tissues. These results suggest that (99m)Tc-EC20 may be clinically useful as a noninvasive radiodiagnostic imaging agent for the detection of FR-positive human cancers.
Leamon
Christopher P
CP
Endocyte, Inc., 1205 Kent Avenue, West Lafayette, Indiana 47906, USA. Leamon@Endocyte.com
Parker
Matthew A
MA
Vlahov
Iontcho R
IR
Xu
Le-Cun
LC
Reddy
Joseph A
JA
Vetzel
Marilynn
M
Douglas
Nikki
N
D000818:Animals; D001692:Biological Transport; D002352:Carrier Proteins / Q000378:metabolism*; D016503:Drug Delivery Systems; D058973:Folate Receptors, GPI-Anchored; D005492:Folic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism* / Q000493:pharmacokinetics; D006801:Humans; D007624:KB Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D009368:Neoplasm Transplantation; D009842:Oligopeptides / Q000138:chemical synthesis / Q000378:metabolism* / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D011956:Receptors, Cell Surface; D013667:Technetium; D014018:Tissue Distribution
D002352:Carrier Proteins; C473829:EC20 folate peptide; D058973:Folate Receptors, GPI-Anchored; D009842:Oligopeptides; D019275:Radiopharmaceuticals; D011956:Receptors, Cell Surface; D013667:Technetium; D005492:Folic Acid