In vivo localization of diglycylcysteine-bearing synthetic peptides by nuclear imaging of oxotechnetate transchelation.

A phenomenon of in vivo transchelation of oxotechnetate from a complex with glucoheptonic acid to synthetic peptides bearing oxotechnetate-binding motifs and a technique for in vivo visualization of these peptides are described. Using two model peptides bearing two tandem diglycylcysteine (GGC) motifs (P1) or three GGC motifs (P2), we demonstrated that: (i) these peptides efficiently transchelated oxo-[99mTc]technetate from a complex with glucoheptonic acid in vitro (a complex with peptides was stable at least 24 h; radiochemical purity exceeded 95% by high performance liquid chromatography); (ii) injection of peptides into the rectus femoris muscle (at 0.5-1 micromol of SH groups) followed by an intravenous injection of 99mTc-glucoheptonate (0.25-0.5 mCi per animal) yielded visualization of the injected muscle by nuclear imaging within 1 h after injection; (iii) the experimental/control (contralateral) thigh muscle ratio was 1.80 +/- 0.05 for peptide P1 and 3.0 +/- 0.1 for P2; (iv) the injection of a control peptide P2 with SH groups covalently modified with N-ethylmaleimide resulted in a ratio of 1.4 +/- 0.2. These findings argue for specific association of oxo-[99mTc]technetate with free thiols within the binding motif of injected peptides in vivo. In vivo transchelation of oxo-[99mTc]technetate may be useful for the purpose of noninvasive imaging of gene expression, i.e., when the expression product bears GGC motifs.