Development of 68Ga-labeled tin colloids for evaluating phagocytic function of Kupffer cells using preclinical PET imaging.

Abstract

This study aimed to investigate the optimal conditions for producing 68Ga-labeled tin colloid and the feasibility of 68Ga-tin colloid positron emission tomography (PET) for visualization and evaluation of the phagocytic function of Kupffer cells (KCs) in vivo. 68Ga-tin colloid was prepared by adding tin solution (1mM, 0.2mL) to 68Ga solution (1.0mL), followed by pH adjustment with sodium acetate (1M, 0.2mL). Various labeling times were tested to find the optimal one. Colloid size was measured by filtering the solution through three-ply membrane filters (with pore sizes of 200, 3000, and 5000nm), and radioactivity was measured in the whole filtrate and the filters using a gamma counter. The in vitro stability of the colloid was evaluated by the size measurement after incubation under ambient conditions for up to 60min. PET scanning was performed for 30min after intravenous administration of 68Ga-tin colloid solution (4MBq) to healthy rats. Time-activity-curves for the liver, spleen, and blood pool were generated. Finally, liver uptake was compared before and after the establishment of KC-depletion and non-alcoholic steatohepatitis (NASH) rat models. Colloid size increased with increasing labeling time. After pH adjustment, the colloid sizes remained nearly unchanged. The optimal labeling time was determined as 30min. PET imaging of healthy rats revealed that liver uptake of the 68Ga-tin colloid increased with increasing colloid size. In KC-depleted rats, liver uptake significantly decreased (n = 4, p < 0.01). NASH model rats showed significantly decreased uptake of 68Ga-tin colloid in the livers (n = 5, p < 0.01). 68Ga-tin colloid, prepared by a simple radiolabeling method, enabled in vivo PET imaging to evaluate the phagocytic function of KCs.