title: Ga-68-labeled neolactosylated human serum albumin (LSA) for PET imaging of hepatic asialoglycoprotein receptor.
abstract: BACKGROUND
  The purpose of this study was the development of (68)Ga-labeled neolactosylated human serum albumin (LSA) for imaging asialoglycoprotein receptors in the liver by using positron emission tomography (PET), which would enable functional imaging with higher resolution than single-photon emission computed tomography (SPECT).
  
  
  METHODS
  LSA was synthesized by conjugating α-lactose to human serum albumin (HSA) by reductive amination. LSA was conjugated with 2-(p-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (SCN-NOTA) and the resultant NOTA-LSA was labeled with (68)Ga at room temperature. The labeling efficiency of NOTA-LSA was evaluated as a function of pH and time. The stability of (68)Ga-NOTA-LSA in phosphate buffered saline (PBS) and human serum at 37 °C was determined. Biodistribution and PET studies of (68)Ga-NOTA-LSA were performed in mice following tail vein injection of radiotracer.
  
  
  RESULTS
  The numbers of lactose and NOTA units per HSA were determined to be 31.7 and 4.6, respectively. When the reaction was done at room temperature, the labeling efficiency of NOTA-LSA was higher than 99% at pH 4.8 and 96% at pH 6. More than 95% of the detected radioactivity was associated with the intact molecule for at least the 4h following synthesis when incubated in PBS or human serum at 37 °C. Biodistribution and animal PET studies showed specific retention of (68)Ga-NOTA-LSA in liver following intravenous administration.
  
  
  CONCLUSIONS
  (68)Ga-NOTA-LSA was successfully developed for imaging asialoglycoprotein receptors in the liver with a simple labeling method, high labeling efficiency, and high stability.
authors.affiliation: Department of Radiology, Duke University Medical Center, Durham, NC, USA.
authors.forename: Jaeyeon
authors.initials: J
authors.lastname: Choi
authors.affiliation: Department of Nuclear Medicine, Institute of Radiation Medicine, Seoul National University College of Medicine, Seoul, South Korea; Department of Radiation Applied Life Science, Seoul National University College of Medicine, Seoul, South Korea; Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea. Electronic address: jmjng@snu.ac.kr.
authors.forename: Jae Min
authors.initials: JM
authors.lastname: Jeong
authors.affiliation: Research Institute, National Cancer Center, Goyang, Gyeonggi, South Korea.
authors.forename: Byong Chul
authors.initials: BC
authors.lastname: Yoo
authors.affiliation: Department of Nuclear Medicine, Institute of Radiation Medicine, Seoul National University College of Medicine, Seoul, South Korea; Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Mi Kyung
authors.initials: MK
authors.lastname: Hong
authors.affiliation: Department of Nuclear Medicine, Institute of Radiation Medicine, Seoul National University College of Medicine, Seoul, South Korea; Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Young Ju
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Department of Nuclear Medicine, Institute of Radiation Medicine, Seoul National University College of Medicine, Seoul, South Korea; Department of Radiation Applied Life Science, Seoul National University College of Medicine, Seoul, South Korea; Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Yun-Sang
authors.initials: YS
authors.lastname: Lee
authors.affiliation: Department of Nuclear Medicine, Institute of Radiation Medicine, Seoul National University College of Medicine, Seoul, South Korea; Department of Radiation Applied Life Science, Seoul National University College of Medicine, Seoul, South Korea; Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Dong Soo
authors.initials: DS
authors.lastname: Lee
authors.affiliation: Department of Nuclear Medicine, Institute of Radiation Medicine, Seoul National University College of Medicine, Seoul, South Korea; Department of Radiation Applied Life Science, Seoul National University College of Medicine, Seoul, South Korea; Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: June-Key
authors.initials: JK
authors.lastname: Chung
mesh_terms: D000818:Animals; D037263:Asialoglycoprotein Receptor / Q000378:metabolism*; D004355:Drug Stability; D005710:Gallium Radioisotopes; D006571:Heterocyclic Compounds / Q000737:chemistry; D006573:Heterocyclic Compounds, 1-Ring; D006801:Humans; D007553:Isotope Labeling; D007785:Lactose / Q000737:chemistry*; D008099:Liver / Q000000981:diagnostic imaging* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008958:Models, Molecular; D049268:Positron-Emission Tomography / Q000379:methods*; D011487:Protein Conformation; D012709:Serum Albumin / Q000737:chemistry* / Q000493:pharmacokinetics
chemical_list: D037263:Asialoglycoprotein Receptor; D005710:Gallium Radioisotopes; D006571:Heterocyclic Compounds; D006573:Heterocyclic Compounds, 1-Ring; D012709:Serum Albumin; C048993:1,4,7-triazacyclononane-N,N',N''-triacetic acid; D007785:Lactose
keywords: Galactose receptor; Gallium-68; Lactose; Liver imaging; NOTA