title: Good manufacturing practice production of [(68)Ga]Ga-ABY-025 for HER2 specific breast cancer imaging.
abstract: Therapies targeting human epidermal growth factor receptor type 2 (HER2) have revolutionized breast cancer treatment, but require invasive biopsies and rigorous histopathology for optimal patient stratification. A non-invasive and quantitative diagnostic method such as positron emission tomography (PET) for the pre-therapeutic determination of the presence and density of the HER2 would significantly improve patient management efficacy and treatment cost. The essential part of the PET methodology is the production of the radiopharmaceutical in compliance with good manufacturing practice (GMP). The use of generator produced positron emitting (68)Ga radionuclide would provide worldwide accessibility of the agent. GMP compliant, reliable and highly reproducible production of [(68)Ga]Ga-ABY-025 with control over the product peptide concentration and amount of radioactivity was accomplished within one hour. Two radiopharmaceuticals were developed differing in the total peptide content and were validated independently. The specific radioactivity could be kept similar throughout the study, and it was 6-fold higher for the low peptide content radiopharmaceutical. Intrapatient comparison of the two peptide doses allowed imaging optimization. The high peptide content decreased the uptake in healthy tissue, in particular liver, improving image contrast. The later imaging time points enhanced the contrast. The combination of high peptide content radiopharmaceutical and whole-body imaging at 2 hours post injection appeared to be optimal for routine clinical use.
authors.affiliation: Section of Nuclear Medicine and PET, PET-Center, Center for Medical Imaging, Department of Surgical Sciences, Uppsala University Uppsala, Sweden.
authors.forename: Irina
authors.initials: I
authors.lastname: Velikyan
authors.affiliation: Affibody AB Solna, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Wennborg
authors.affiliation: Affibody ABSolna, Sweden; Department of Immunology, Genetics and PathologyUppsala, Sweden.
authors.forename: Joachim
authors.initials: J
authors.lastname: Feldwisch
authors.affiliation: Department of Immunology, Genetics and Pathology Uppsala, Sweden.
authors.forename: Henrik
authors.initials: H
authors.lastname: Lindman
authors.affiliation: Department of Immunology, Genetics and Pathology Uppsala, Sweden.
authors.forename: Jörgen
authors.initials: J
authors.lastname: Carlsson
authors.affiliation: Section of Nuclear Medicine and PET, PET-Center, Center for Medical Imaging, Department of Surgical Sciences, Uppsala University Uppsala, Sweden.
authors.forename: Jens
authors.initials: J
authors.lastname: Sörensen
keywords: Affibody; GMP; Gallium-68; HER2; breast cancer; clinical study