Abstract
1479
Objectives Peptides used in synthesis of radiopharmaceutical PET tracers are often lipophilic and adhere to the walls of container closure systems (CCS) such that the peptide and product is unrecoverable after synthesis occurs. This investigation compares an FDA approved USP Type I borosilicate glass CCS to a novel Crystal Zenith Resin CCS (Daikyo Seiko), to evaluate the losses due to container surface adherence of 68Gallium and 68Ga-DOTATOC (68Gallium-Edotreotide, 68Gallium- DOTA-D-Phe1-Tyr3-octreotide) after synthesis.
Methods 68Ga-DOTATOC synthesis was conducted by adding 68Ga-chloride (68Ga generator, iTHEMBA), 2M HEPES (4-(2-Hydroxyethyl)piperazine-1-ethanesulfonic acid, Sigma Aldrich) or 2M Sodium Acetate (Sigma Aldrich), and 5µg to 30µg of DOTATOC (DOTA-DPhe1-Tyr3-octreotide, Bachem), into the crystal resin or glass CCS. The reaction mixture was heated for 15 minutes, and then cooled to room temperature. The crude reaction mixture was withdrawn via syringe for final processing. The CCS was then assayed using a dose calibrator to determine the amount of retained 68Ga-DOTATOC.
Results In all experiments, with peptide amounts ranging from 5µg to 30µg and for both HEPES and Sodium Acetate buffering systems, the crystal resin CCS retained less residual activity than the glass CCS, resulting in higher recovery of the product. Using 2M HEPES and 5µg of DOTATOC, the glass and crystal resin CCS retained 6.2% and 1.3%, respectively (n=3 each). Utilizing a 2M Sodium Acetate buffering system with 30µg of DOTATOC the glass and crystal resin retained 6.1% and 3.2% respectively (n=3 each). Product yield was equivalent under the same reaction conditions independent of heating in the glass or crystal resin CCS. Both the crystal resin and glass vials showed no retention of 68Ga (n=8 each).
Conclusions For applications utilizing limited or expensive peptides, the crystal resin CCS allows substantially higher recovery with unvarying product yields compared with glass CSS.
Research Support Supported through a grant provided by West Pharmaceutical Services, Inc