Asialoglycoprotein receptors (ASGP-R) are well known to exist on the mammalian liver, situate on the surface of hepatocyte membrane. Quantitative imaging of asialoglycoprotein receptors could estimate the function of the liver. (99m)Tc labeled galactosyl-neoglycoalbumin (NGA) and diethylenetriaminepentaacetic acid galactosyl human serum albumin (GSA) have been developed for SPECT imaging and clinical used in Japan. In this study, we labeled the NGA with (18)F to get a novel PET tracer [(18)F]FNGA and evaluated its hepatic-targeting efficacy and pharmacokinetics.
Methods: NGA was labeled with (18)F by conjugation with N-succinimidyl-4-(18)F-fluorobenzoate ([(18)F]SFB) under a slightly basic condition. The in vivo metabolic stability of [(18)F]FNGA was determined. Ex vivo biodistribution of [(18)F]FNGA and blocking experiment was investigated in normal mice. MicroPET images were acquired in rat with and without block at 5 min and 15 min after injection of the radiotracer (3.7MBq/rat), respectively.
Results: Starting with (18)F(-) Kryptofix 2.2.2./K(2)CO(3) solution, the total reaction time for [(18)F]FNGA is about 150 min. Typical decay-corrected radiochemical yield is about 8-10%. After rapid purified with HiTrap desalting column, the radiochemical purity of [(18)F]FNGA was more than 99% determined by radio-HPLC. [(18)F]FNGA was metabolized to produce [(18)F]FB-Lys in urine at 30 min. Ex vivo biodistribution in mice showed that the liver accumulated 79.18+/-7.17% and 13.85+/-3.10% of the injected dose per gram at 5 and 30 min after injection, respectively. In addition, the hepatic uptake of [(18)F]FNGA was blocked by pre-injecting free NGA as blocking agent (18.55+/-2.63%ID/g at 5 min pi), indicating the specific binding to ASGP receptor. MicroPET study obtained quality images of rat at 5 and 15 min post-injection.
Conclusion: The novel ASGP receptor tracer [(18)F]FNGA was synthesized with high radiochemical yield. The promising biological properties of [(18)F]FNGA afford potential applications for assessment of hepatocyte function in the future. It may provide quantitative information and better resolution which particularly help to the liver surgery.