TY - JOUR T1 - Copolymer-Based Hepatocyte Asialoglycoprotein Receptor Targeting Agent for SPECT JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 978 LP - 985 DO - 10.2967/jnumed.110.085167 VL - 52 IS - 6 AU - Wenjiang Yang AU - Tiantian Mou AU - Guoqiang Shao AU - Feng Wang AU - Xianzhong Zhang AU - Boli Liu Y1 - 2011/06/01 UR - http://jnm.snmjournals.org/content/52/6/978.abstract N2 - 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 99mTc 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 99mTc using tricine as a coligand. Then 99mTc[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: 99mTc[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 99mTc. The promising biologic properties of 99mTc[P(VLA-co-VNI)](tricine)2 afford potential applications for the assessment of hepatocyte function in the future. ER -