title: Optimization of hapten-peptide labeling for pretargeted immunoPET of bispecific antibody using generator-produced 68Ga.
abstract: Bispecific antibody pretargeting is highly sensitive and specific for cancer detection by PET. In this study, the preparation of a high-specific-activity (68)Ga-labeled hapten-peptide, IMP288, was evaluated.
  
  
  METHODS
  IMP288 (DOTA-D-Tyr-D-Lys(histamine-succinyl-glycine [HSG])-D-glu-D-Lys(HSG)-NH(2)) was added to buffered (68)Ga and then heated in boiling water and purified on a reversed-phase cartridge. Tumor-bearing nude mice were used for biodistribution and tumor localization studies.
  
  
  RESULTS
  (68)Ga-IMP288 was prepared at a starting specific activity up to 1.78 GBq/nmol, with final yields of 0.74 GBq/nmol (decay-corrected) and less than 1% unbound (68)Ga. Purification was essential to remove unbound (68)Ga and (68)Ge breakthrough. Pretargeted animals showed a high (68)Ga-IMP288 uptake (27.5 ± 5.8 percentage injected dose per gram), with ratios of 13.6 ± 4.8, 66.8 ± 14.5, and 325.9 ± 61.9 for the kidneys, liver, and blood, respectively, at 1.5 h after peptide injection.
  
  
  CONCLUSIONS
  High-specific-activity labeling of DOTA-hapten-peptide was obtained from the (68)Ga/(68)Ge generator for approximately 1 y, yielding products suitable for immunoPET.
authors.affiliation: Center for Molecular Medicine and Immunology and the Garden State Cancer Center, Belleville, New Jersey 07109, USA.
authors.forename: Habibe
authors.initials: H
authors.lastname: Karacay
authors.forename: Robert M
authors.initials: RM
authors.lastname: Sharkey
authors.forename: William J
authors.initials: WJ
authors.lastname: McBride
authors.forename: Edmund A
authors.initials: EA
authors.lastname: Rossi
authors.forename: Chien-Hsing
authors.initials: CH
authors.lastname: Chang
authors.forename: David M
authors.initials: DM
authors.lastname: Goldenberg
mesh_terms: D000818:Animals; D018033:Antibodies, Bispecific; D002851:Chromatography, High Pressure Liquid; D005710:Gallium Radioisotopes / Q000493:pharmacokinetics; D019073:HT29 Cells; D006207:Half-Life; D006241:Haptens / Q000737:chemistry*; D006573:Heterocyclic Compounds, 1-Ring / Q000493:pharmacokinetics; D006801:Humans; D007205:Indium Radioisotopes; D007553:Isotope Labeling; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009842:Oligopeptides / Q000493:pharmacokinetics; D010455:Peptides / Q000737:chemistry*; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: D018033:Antibodies, Bispecific; C515662:DOTA-tyrosyl-lysyl(histaminyl-succinyl-glycyl)-glutamyl-lysyl(histaminyl-succinyl-glycyl)amide; D005710:Gallium Radioisotopes; D006241:Haptens; D006573:Heterocyclic Compounds, 1-Ring; D007205:Indium Radioisotopes; D009842:Oligopeptides; D010455:Peptides; D019275:Radiopharmaceuticals