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

$^{111}$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 $^{111}$Ag-labeled molecules will significantly affect the PAC spectra. Here we illustrate this effect, by simulating $^{111}$Ag PAC spectra for $^{111}$Ag-labeled molecules with molecular masses spanning from$ 10^2$ to $10^6$ 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 $^{111}$Ag-PAC data obtained from a pilot study involving $^{111}$Ag(I) bound to a designed chelator exhibiting fast reorientation in solution, as well as to $^{111}$Ag-labeled species formed by $^{111}$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 111Ag-labeled compounds. Potential in vivo applications are stability studies of $^{111}$Ag-radiopharmaceuticals, dissociation studies of $^{111}$Ag from the labeled molecule followed by binding to another (bio)molecule, or binding of $^{111}$Ag-labeled probes to larger carriers such as proteins.