title: Synthesis and in vivo evaluation of gallium-68-labeled glycine and hippurate conjugates for positron emission tomography renography.
abstract: The objective of this study was to evaluate four new (68) Ga-labeled 1,4,7,10-cyclododeca-1,4,7,10-tetraacetic acid (DOTA)/1,4,7-triazacyclononane-1,4,7-triacetic acid derived (NODAGA)-glycine/hippurate conjugates and select a lead candidate for potential application in positron emission tomography (PET) renography. The non-metallated conjugates were synthesized by a solid phase peptide synthesis method. The (68) Ga labeling was achieved by reacting an excess of the non-metallated conjugate with (68) GaCl4 (-) at pH -4.5 and 10-min incubation either at room temperature for NODAGA or 90 °C for DOTA. Radiochemical purity of all (68) Ga conjugates was found to be >98%. (68) Ga-NODAGA-glycine displayed the lowest serum protein binding (0.4%) in vitro among the four (68) Ga conjugates. Biodistribution of (68) Ga conjugates in healthy Sprague Dawley rats at 1-h post-injection revealed an efficient clearance from circulation primarily through the renal-urinary pathway with <0.2% of injected dose per gram remaining in the blood. The kidney/blood and kidney/muscle ratios of (68) Ga-NODAGA-glycine were significantly higher than other (68) Ga conjugates. On the basis of these results, (68) Ga-NODAGA-glycine was selected as the lead candidate. (68) Ga-NODAGA-glycine PET renograms obtained in healthy rats suggest (68) Ga-NODAGA-glycine as a PET alternate of (99m) Tc-Diethylenetriaminepentaacetic acid (DTPA).
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: Gopal
authors.initials: G
authors.lastname: Pathuri
authors.forename: Andria F
authors.initials: AF
authors.lastname: Hedrick
authors.forename: Spenser E
authors.initials: SE
authors.lastname: January
authors.forename: Wendy K
authors.initials: WK
authors.lastname: Galbraith
authors.forename: Vibhudutta
authors.initials: V
authors.lastname: Awasthi
authors.forename: Charles D
authors.initials: CD
authors.lastname: Arnold
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Cowley
authors.forename: Hariprasad
authors.initials: H
authors.lastname: Gali
mesh_terms: D000085:Acetates / Q000737:chemistry; D000818:Animals; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D005260:Female; D005998:Glycine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D006573:Heterocyclic Compounds, 1-Ring / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*; D006626:Hippurates / Q000737:chemistry*; D049268:Positron-Emission Tomography; D011866:Radioisotope Renography; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
chemical_list: C572723:1-(1,3-carboxypropyl)-4,7-carboxymethyl-1,4,7-triazacyclononane; C000602448:68Ga-NODAGA-glycine; D000085:Acetates; D056831:Coordination Complexes; D006573:Heterocyclic Compounds, 1-Ring; D006626:Hippurates; D019275:Radiopharmaceuticals; C030514:hippuric acid; D005998:Glycine
keywords: PET; gallium-68; radiopharmaceuticals; renography