title: Radiolabeling and Preliminary Evaluation of Ga-68 Labeled NODAGA-Ubiquicidin Fragments for Prospective Infection Imaging.
abstract: The present work was aimed at the development of prospective positron emission tomography (PET) agents for infection imaging. Towards this aim, ubiquicidin (UBI) fragments conjugated with the macrocyclic NODAGA chelator were radiolabeled with Ga-68 and evaluated.
  
  
  
  Conformations of custom synthesized NODAGA-UBI (29-41) and NODAGA-UBI (31-38) conjugates were compared with UBI (29-41) by circular dichroism (CD) spectroscopy. Optimization of labeling of NODAGA conjugates of UBI peptides with Ga-68 was performed and quality control analysis was carried out by chromatography techniques. In vitro uptake of [68Ga] NODAGA-UBI (29-41) and [68Ga]NODAGA-UBI (31-38) was studied in Staphylococcus aureus cells. In vivo distribution of [68Ga]GaCl3and [68Ga]NODAGA-UBI complexes was performed in normal Swiss mice.
  
  
  
  Conformations of NODAGA-UBI (29-41) and NODAGA-UBI (31-38) conjugates were found to be similar to UBI (29-41). NODAGA-UBI conjugates could be consistently labeled with Ga-68 in high radiochemical yields (>95 %) with high radiochemical purity (>95 %). [68Ga]NODAGA-UBI (29-41) and [68Ga]NODAGA-UBI (31-38) complexes showed retention time of 14 and 14.5 min, respectively, by HPLC radiochromatogram. Specific uptake of [68Ga]NODAGA-UBI fragments was observed in S.aureus cells. Greater than 64 % of the injected dose was cleared via the renal route at 1 h post injection, and no significant uptake in vital organs of mice was observed with both the agents.
  
  
  
  This is the first report on Ga-68 labeled NODAGA-UBI fragments for infection imaging and the agents hold tremendous prospect in PET imaging.
authors.affiliation: Radiopharmaceuticals Evaluation Section, Isotope Production & Applications Division, Bhabha Atomic Research Centre, Mumbai, 400 085, India.
authors.forename: Jyotsna
authors.initials: J
authors.lastname: Bhatt
authors.affiliation: Radiopharmaceuticals Evaluation Section, Isotope Production & Applications Division, Bhabha Atomic Research Centre, Mumbai, 400 085, India. archanas@barc.gov.in.
authors.forename: Archana
authors.identifier: 0000-0003-3068-1890
authors.initials: A
authors.lastname: Mukherjee
authors.affiliation: Radiopharmaceuticals Evaluation Section, Isotope Production & Applications Division, Bhabha Atomic Research Centre, Mumbai, 400 085, India.
authors.forename: Aruna
authors.initials: A
authors.lastname: Korde
authors.affiliation: Solid State Physics Division, Bhabha Atomic Research Centre (BARC), Mumbai, 400 085, India.
authors.forename: Mukesh
authors.initials: M
authors.lastname: Kumar
authors.affiliation: Radiation Biology & Health Sciences Division, Bhabha Atomic Research Centre (BARC), Mumbai, 400 085, India.
authors.forename: Haladhar Dev
authors.initials: HD
authors.lastname: Sarma
authors.affiliation: Radiopharmaceuticals Evaluation Section, Isotope Production & Applications Division, Bhabha Atomic Research Centre, Mumbai, 400 085, India.
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Dash
mesh_terms: D000085:Acetates / Q000737:chemistry*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D002942:Circular Dichroism; D056831:Coordination Complexes / Q000737:chemistry; D003952:Diagnostic Imaging / Q000379:methods*; D005710:Gallium Radioisotopes / Q000737:chemistry*; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry*; D051379:Mice; D010455:Peptides / Q000737:chemistry; D019275:Radiopharmaceuticals / Q000737:chemistry*; D012269:Ribosomal Proteins / Q000737:chemistry*; D013203:Staphylococcal Infections / Q000175:diagnosis* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000502:physiology; D014018:Tissue Distribution
chemical_list: C572723:1-(1,3-carboxypropyl)-4,7-carboxymethyl-1,4,7-triazacyclononane; C000615618:68Ga-DOTA ubiquicidin; D000085:Acetates; D056831:Coordination Complexes; D005710:Gallium Radioisotopes; D006573:Heterocyclic Compounds, 1-Ring; D010455:Peptides; D019275:Radiopharmaceuticals; D012269:Ribosomal Proteins; C040469:ribosomal protein S30
keywords: Antimicrobial peptides; Ga-68 radiopharmaceuticals; Infection Imaging; PET Imaging; [68Ga]NODAGA-UBI (29–41); [68Ga]NODAGA-UBI (31–38)