Towards in vivo applications of Ag perturbed angular correlation of γ-rays (PAC) spectroscopy.

Ag-perturbed angular correlation of γ-rays (PAC) spectroscopy provides information on the nuclear quadrupole interactions, and thereby on the local structure and dynamics of the silver ion binding site. Brownian rotational motion, i.e. rotational diffusion, of Ag-labeled molecules will significantly affect the PAC spectra. Here we illustrate this effect, by simulating Ag PAC spectra for Ag-labeled molecules with molecular masses spanning from 10 to 10 g/mol, reflecting a span from fast (small molecules) to slow (large molecules) rotational diffusion on the PAC time scale. The simulated spectra are compared to Ag-PAC data obtained from a pilot study involving Ag(I) bound to a designed chelator exhibiting fast reorientation in solution, as well as to Ag-labeled species formed by Ag(I) in human serum, exhibiting slow (or no) reorientation on the PAC time scale. The simulated and experimental data illustrate typical PAC signals that are likely to be observed in vivo, when following the fate of Ag-labeled compounds. Potential in vivo applications are stability studies of Ag-radiopharmaceuticals, dissociation studies of Ag from the labeled molecule followed by binding to another (bio)molecule, or binding of Ag-labeled probes to larger carriers such as proteins.