Metallothionein: a bifunctional chelator for the radiolabeling of biologically active molecules.

Abstract

Cysteine-rich metallothionein has been shown to bind as many as seven TcO3+ cores in TcO (Cys) units which adopt square-base pyramidal geometry. The Tc atoms in 99mTc,Zn-MT and 99mTc,Zn-MT-MAb species formed in the exchange reaction with the labile 99mTcO (glucoheptonate) complex are stable to oxidation and transchelation in vivo. The kinetics of labeling with the carrier-free radionuclide 99mTc are diffusion-limited at MT concentrations below 10(-5) M. Zinc-MT-MAb conjugates can be efficiently radiolabeled at concentrations greater than or equal to 10(-5) M. The conjugation of MT to tumor specific MAb's has been accomplished with the preservation of the in vivo tumor targeting capability of the MAb and the excellent metal-binding properties of MT. The success achieved in this research demonstrates the potential of metallothionein as a carrier of medically useful metallic radionuclides in labeling of important biologically active molecules.