Fluorine-18 labeled galactosyl-neoglycoalbumin for imaging the hepatic asialoglycoprotein receptor |
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Authors: | Wenjiang Yang Tiantian Mou Cheng Peng Zhanhong Wu Xianzhong Zhang Fang Li Yunchuan Ma |
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Institution: | aKey Laboratory of Radiopharmaceuticals (Beijing Normal University), Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, PR China;bPET Center of Xuanwu Hospital, Capital Medical University, Beijing 100053, PR China;cDepartment of Nuclear Medicine, PUMC Hospital, CAMS and PUMC, Beijing 100730, PR China |
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Abstract: | 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. 99mTc 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 18F to get a novel PET tracer 18F]FNGA and evaluated its hepatic-targeting efficacy and pharmacokinetics. Methods: NGA was labeled with 18F by conjugation with N-succinimidyl-4-18F-fluorobenzoate (18F]SFB) under a slightly basic condition. The in vivo metabolic stability of 18F]FNGA was determined. Ex vivo biodistribution of 18F]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 (3.7 MBq/rat), respectively. Results: Starting with 18F− Kryptofix 2.2.2./K2CO3 solution, the total reaction time for 18F]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 18F]FNGA was more than 99% determined by radio-HPLC. 18F]FNGA was metabolized to produce 18F]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 18F]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 18F]FNGA was synthesized with high radiochemical yield. The promising biological properties of 18F]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. |
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Keywords: | 18F NGA [18F]FNGA PET imaging Asialoglycoprotein receptor |
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