title: Development of ⁶⁸Ga-labelled DTPA galactosyl human serum albumin for liver function imaging.
abstract: OBJECTIVE
  The hepatic asialoglycoprotein receptor is responsible for degradation of desialylated glycoproteins through receptor-mediated endocytosis. It has been shown that imaging of the receptor density using [(99m)Tc]diethylenetriamine pentaacetic acid (DTPA) galactosyl human serum albumin ([(99m)Tc]GSA) allows non-invasive determination of functional hepatocellular mass. Here we present the synthesis and evaluation of [(68)Ga]GSA for the potential use with positron emission tomography (PET).
  
  
  METHODS
  Labelling of GSA with (68)Ga was carried out using a fractionated elution protocol. For quality control thin-layer chromatography (TLC), high-performance liquid chromatography (HPLC) and size exclusion chromatography (SEC) techniques were evaluated. Stability of [(68)Ga]GSA was studied in phosphate-buffered saline (PBS) and human serum. For in vivo evaluation [(68)Ga]GSA distribution in Lewis rats was compared with [(99m)Tc]GSA by using a dual isotope protocol. PET and planar imaging studies were performed using the same scaled molar dose of [(68)Ga]GSA and [(99m)Tc]GSA. Time-activity curves (TAC) for heart and liver were generated and corresponding parameters calculated (t50, t90).
  
  
  RESULTS
  [(68)Ga]GSA can be produced with high radiochemical purity. The best TLC methods for determining potential free (68)Ga include 0.1 M sodium citrate as eluent. None of the TLC methods tested were able to determine potential colloids. This can be achieved by SEC. HPLC confirmed high radiochemical purity (>98%). Stability after 120 min incubation at 37 °C was high in PBS (>95% intact tracer) and low in human serum (∼27% intact tracer). Biodistribution studies simultaneously injecting both tracers showed comparable liver uptake, whereas activity concentration in blood was higher for [(68)Ga]GSA compared to [(99m)Tc]GSA. The [(99m)Tc]GSA TACs exhibited a small degree of hepatic metabolism compared to the [(68)Ga]GSA curves. The mean [(68)Ga]GSA t90 was higher than the mean t90 for [(99m)Tc]GSA. The mean [(68)Ga]GSA t50 was not significantly different from the mean t50 for [(99m)Tc]GSA.
  
  
  CONCLUSIONS
  This study provides a promising new (68)Ga-labelled compound based on a commercially used kit for imaging the functional hepatocellular mass.
authors.affiliation: Department of Nuclear Medicine, Innsbruck Medical University, Innsbruck, Austria. roland.haubner@i-med.ac.at
authors.forename: Roland
authors.initials: R
authors.lastname: Haubner
authors.forename: David R
authors.initials: DR
authors.lastname: Vera
authors.forename: Salman
authors.initials: S
authors.lastname: Farshchi-Heydari
authors.forename: Anna
authors.initials: A
authors.lastname: Helbok
authors.forename: Christine
authors.initials: C
authors.lastname: Rangger
authors.forename: Daniel
authors.initials: D
authors.lastname: Putzer
authors.forename: Irene J
authors.initials: IJ
authors.lastname: Virgolini
mesh_terms: D000418:Albumins / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D005710:Gallium Radioisotopes / Q000737:chemistry* / Q000493:pharmacokinetics; D006801:Humans; D008099:Liver / Q000000981:diagnostic imaging*; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D004369:Pentetic Acid / Q000737:chemistry; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D051381:Rats; D013668:Technetium Tc 99m Aggregated Albumin / Q000493:pharmacokinetics; D016284:Technetium Tc 99m Pentetate / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: C586083:68Ga-labelled DTPA galactosyl human serum albumin; D000418:Albumins; D005710:Gallium Radioisotopes; D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; D013668:Technetium Tc 99m Aggregated Albumin; C070561:technetium Tc 99m DTPA-galactosyl-human serum albumin; D004369:Pentetic Acid; D016284:Technetium Tc 99m Pentetate