Poly(vinylbenzyl-O-β-D-galactopyranosyl-D-gluconamide) (PVLA) can be specifically internalized by hepatocytes via the asialoglycoprotein receptor. In this study, we synthesized and characterized galactose-carrying copolymers with hydrazinonicotinamide chains as bifunctional groups to radiolabel PVLA with (99m)Tc for SPECT targeting specific hepatocytes.
Methods: Poly(N-p-vinylbenzyl-[O-β-D-galactopyranosyl-(1→4)-D-gluconamide]-co-N-p-vinylbenzyl-6-[2-(4-dimethylamino)benzaldehydehydrazono]nicotinate) (P(VLA-co-VNI)) was first prepared via copolymerization of N-p-vinylbenzyl-O-β-D-galactopyranosyl-D-gluconamide with 5% (mol) of N-p-vinylbenzyl-(4-dimethylaminobenzaldehyde hydrazono)nicotinamide. The copolymer was labeled with (99m)Tc using tricine as a coligand. Then (99m)Tc[P(VLA-co-VNI)](tricine)(2) was evaluated by in vivo metabolic stability and biodistribution in normal mice. SPECT was performed in normal New Zealand White rabbits and rabbits with liver cancer.
Results: (99m)Tc[P(VLA-co-VNI)](tricine)(2) was prepared in high labeling yield (>95%) and radiochemical purity (>99%), with good stability. The results of biodistribution in mice demonstrated that the liver uptake was 125.33 ± 10.99 percentage injected dose per gram at 10 min after injection and could be blocked significantly by preinjecting free neogalactosylalbumin or P(VLA-co-VNI). SPECT images with high quality were obtained at 15, 30, 60, and 120 min after injection of the radiotracer. Significant radioactivity defect was observed in the liver cancer model.
Conclusion: The bifunctional coupling agent hydrazinonicotinamide was introduced to PVLA via copolymerization and labeled with (99m)Tc. The promising biologic properties of (99m)Tc[P(VLA-co-VNI)](tricine)(2) afford potential applications for the assessment of hepatocyte function in the future.