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

Objective: 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. Methods: ⁶⁸Ga-tin colloid was prepared by adding tin solution (1 mM, 0.2 mL) to ⁶⁸Ga solution (1.0 mL), followed by pH adjustment with sodium acetate (1 M, 0.2 mL). 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 5000 nm), 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 60 min. PET scanning was performed for 30 min after intravenous administration of ⁶⁸Ga-tin colloid solution (4 MBq) 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. Results: Colloid size increased with increasing labeling time. After pH adjustment, the colloid sizes remained nearly unchanged. The optimal labeling time was determined as 30 min. 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). Conclusions: ⁶⁸Ga-tin colloid, prepared by a simple radiolabeling method, enabled in vivo PET imaging to evaluate the phagocytic function of KCs.