Labeling Cyclic Glycoprotein IIb/IIIa Receptor Antagonists with 99mTc by the Preformed Chelate Approach: Effects of Chelators on Properties of [99mTc]Chelator−Peptide Conjugates

Abstract
Several cyclic GPIIb/IIIa receptor antagonists were labeled with 99mTc by the preformed chelate approach using chelators such as H 4 L1 [4,5-bis(mercaptoacetamido)pentanoic acid], H 4 L2 [3,4-bis(mercaptoacetamido)benzoic acid], H 3 L3 [2-(mercapto)ethylaminoacetyl-l-cysteine], H 4 L4 [N-(mercaptoacetyl)glycylglycylglycine], H 4 L5 [N-[2-(mercapto)propionyl]glycylglycylglycine], and H 4 L6 [N-[2-(mercapto)propionyl]glycylglycyl-γ-aminobutyric acid]. In this approach, the [99mTc]chelator complexes are formed first, followed by the activation of the carboxylic group on the complex by formation of its tetrafluorophenol (TFP) ester and the conjugation of the TFP ester with an amino group of a cyclic GPIIb/IIIa receptor antagonist. The 99mTc-labeled cyclic GPIIb/IIIa receptor antagonists were characterized by radio-HPLC (high-performance liquid chromatography); differences in lipophilicity of the [99mTc]chelator−peptide conjugate are attributable to the effects of both the cyclic peptide and the chelator.