Towards in vivo applications of ¹¹¹Ag perturbed angular correlation of γ-rays (PAC) spectroscopy

¹¹¹Ag-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 ¹¹¹Ag-labeled molecules will significantly affect the PAC spectra. Here we illustrate this effect, by simulating ¹¹¹Ag PAC spectra for ¹¹¹Ag-labeled molecules with molecular masses spanning from 10² to 10⁶ 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 ¹¹¹Ag-PAC data obtained from a pilot study involving ¹¹¹Ag(I) bound to a designed chelator exhibiting fast reorientation in solution, as well as to ¹¹¹Ag-labeled species formed by ¹¹¹Ag(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 ¹¹¹Ag-labeled compounds. Potential in vivo applications are stability studies of ¹¹¹Ag-radiopharmaceuticals, dissociation studies of ¹¹¹Ag from the labeled molecule followed by binding to another (bio)molecule, or binding of ¹¹¹Ag-labeled probes to larger carriers such as proteins.