title: A container closure system that allows for greater recovery of radiolabeled peptide compared to the standard borosilicate glass system.
abstract: OBJECTIVE
  Often peptides used in synthesis of radiopharmaceutical PET tracers are lipophilic and adhere to the walls of container closure systems (CCS) such that costly peptide and product are not fully recoverable after synthesis occurs. This investigation compares a standard United States Pharmacopeia (USP) Type I borosilicate glass CCS to a cyclic polyolefin copolymer Crystal Zenith(®) (CZ) CCS, for (68)Ga-chloride and (68)Ga-DOTATOC ([(68)Ga] Ga-DOTA-D-Phe1-Tyr3-octreotide) retention in the reaction vial after labeling.
  
  
  METHODS
  (68)Gallium labeling of DOTATOC was conducted by adding (68)Ga-chloride, 2M HEPES (4-(2-hydroxyethyl)piperazine-1-ethanesulfonic acid) or 0.75 M sodium acetate, and 1-30 µg of DOTATOC into the CZ or glass CCS. The reaction mixture was heated for 15 min and cooled to room temperature. The crude reaction mixture was then withdrawn via syringe, for final processing. The CCS was then assayed using a dose calibrator to determine the amount of retained (68)Ga-DOTATOC. Statistical significance was assessed using an unpaired Student's t-test.
  
  
  RESULTS
  In all experiments (n=72) with various amounts of peptide and different buffering systems, the CZ CCS retained less activity than the glass CCS. Using 2 M HEPES and 15 µg or 30 µg of DOTATOC, the CZ CCS retained approximately 10% less of the labeled DOTATOC compared to the glass CCS (p<0.05). Utilizing either a sodium acetate or a HEPES buffering system with 15 µg or 30 µg of DOTATOC, the CZ CCS retained approximately 2.5% less of the total reaction activity compared to the glass CCS (p<0.05). Product yield was equivalent in glass and CZ CCS under the same reaction conditions. Both the CZ and glass vials showed no retention of (68)Ga-chloride.
  
  
  CONCLUSIONS
  For applications involving the labeling of peptides such as (68)Ga-DOTATOC, the CZ CCS compared to the glass CCS, results in an improved recovery of product.
authors.affiliation: Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA.
authors.forename: Alicia K
authors.initials: AK
authors.lastname: Leece
authors.forename: Pedram
authors.initials: P
authors.lastname: Heidari
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Yokell
authors.forename: Umar
authors.initials: U
authors.lastname: Mahmood
mesh_terms: D001896:Boron Compounds / Q000737:chemistry*; D005710:Gallium Radioisotopes / Q000737:chemistry*; D005898:Glass; D010455:Peptides / Q000737:chemistry / Q000302:isolation & purification*; D017640:Silicates / Q000737:chemistry*
chemical_list: D001896:Boron Compounds; D005710:Gallium Radioisotopes; D010455:Peptides; D017640:Silicates
keywords: (68)Ga-DOTATOC; Crystal resin closure system; Peptide adsorption; Recovery