title: [68Ga]NOTA-Galactosyl Human Serum Albumin: a Tracer for Liver Function Imaging with Improved Stability.
abstract: OBJECTIVE
  Non-invasive techniques allowing quantitative determination of the functional liver mass are of great interest for patient management in a variety of clinical settings. Recently, we presented [68Ga]DTPA-GSA to target the hepatic asialoglycoprotein receptor for this purpose. Here, we introduce [68Ga]NOTA-GSA to improve metabolic stability of the radiopharmaceutical and compare the imaging properties with [68Ga]DTPA-GSA.
  
  
  METHODS
  Labeling of the compounds was carried out at room temperature using 1.9 M sodium acetate as buffer. For quality control, thin-layer, high-performance liquid, and size exclusion chromatographies were used. Metabolic stability was studied in rat and human serums. For in vivo evaluation, Fischer rats were scanned by positron emission tomography and magnetic resonance imaging and subsequently sacrificed for biodistribution studies. Time activity curves (TACs) for heart and liver were generated and corresponding parameters (T50, T90, LHL15, HH15) were calculated.
  
  
  RESULTS
  [68Ga]NOTA-GSA can be produced in high radiochemical yield and purity (>95 %) within 15 min. Stability studies revealed almost no metabolite formation over the 2-h observation period. Analysis of the TACs showed comparable results for most of the investigated parameters. The only significant difference was found in the T90value, where [68Ga]NOTA-GSA showed slower uptake in comparison with68Ga-DTPA-GSA (123 ± 10 vs. 89 ± 3 s, p < 0.01).
  
  
  CONCLUSIONS
  [68Ga]NOTA-GSA showed a significant increase of the metabolic stability and in most organs lower background activity. However, comparison of LHL15 and HH15 indicates that the increased stability did not further improve the diagnostic value. Thus, [68Ga]NOTA-GSA and [68Ga]DTPA-GSA can be used equivalent for imaging hepatic function with positron emission tomography.
authors.affiliation: Department of Nuclear Medicine, Medical University of Innsbruck, Anichstr. 35, 6020, Innsbruck, Austria. roland.haubner@i-med.ac.at.
authors.forename: Roland
authors.identifier: http://orcid.org/0000-0002-4665-7433
authors.initials: R
authors.lastname: Haubner
authors.affiliation: Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Röntgenweg 13, 72076, Tübingen, Germany.
authors.forename: Andreas M
authors.initials: AM
authors.lastname: Schmid
authors.affiliation: Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Röntgenweg 13, 72076, Tübingen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Maurer
authors.affiliation: Department of Nuclear Medicine, Medical University of Innsbruck, Anichstr. 35, 6020, Innsbruck, Austria.
authors.forename: Christine
authors.initials: C
authors.lastname: Rangger
authors.affiliation: Department of Nuclear Medicine, Medical University of Innsbruck, Anichstr. 35, 6020, Innsbruck, Austria.
authors.forename: Llanos Geraldo
authors.initials: LG
authors.lastname: Roig
authors.affiliation: Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Röntgenweg 13, 72076, Tübingen, Germany.
authors.forename: Bernd J
authors.initials: BJ
authors.lastname: Pichler
authors.affiliation: Department of Nuclear Medicine, Medical University of Innsbruck, Anichstr. 35, 6020, Innsbruck, Austria.
authors.forename: Irene J
authors.initials: IJ
authors.lastname: Virgolini
mesh_terms: D000818:Animals; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry*; D005682:Gadolinium / Q000737:chemistry*; D006801:Humans; D008099:Liver / Q000502:physiology*; D008111:Liver Function Tests; D008297:Male; D057054:Molecular Imaging / Q000379:methods*; D004369:Pentetic Acid / Q000737:chemistry; D011916:Rats, Inbred F344; D000075462:Serum Albumin, Human / Q000737:chemistry*; D014018:Tissue Distribution
chemical_list: D056831:Coordination Complexes; D004369:Pentetic Acid; D005682:Gadolinium; D000075462:Serum Albumin, Human
keywords: Galactosyl human serum albumin; Gallium-68; Liver function imaging; Nota; Positron emission tomography