Automated cassette-based production of high specific activity [203/212Pb]peptide-based theranostic radiopharmaceuticals for image-guided radionuclide therapy for cancer.

Applied Radiation and Isotopes : Including Data, Instrumentation and Methods for Use in Agriculture, Industry and Medicine
Mengshi LiMichael K Schultz

Abstract

A method for preparation of Pb-212 and Pb-203 labeled chelator-modified peptide-based radiopharmaceuticals for cancer imaging and radionuclide therapy has been developed and adapted for automated clinical production. Pre-concentration and isolation of radioactive Pb2+ from interfering metals in dilute hydrochloric acid was optimized using a commercially-available Pb-specific chromatography resin packed in disposable plastic columns. The pre-concentrated radioactive Pb2+ is eluted in NaOAc buffer directly to the reaction vessel containing chelator-modified peptides. Radiolabeling was found to proceed efficiently at 85°C (45min; pH 5.5). The specific activity of radiolabeled conjugates was optimized by separation of radiolabeled conjugates from unlabeled peptide via HPLC. Preservation of bioactivity was confirmed by in vivo biodistribution of Pb-203 and Pb-212 labeled peptides in melanoma-tumor-bearing mice. The approach has been found to be robustly adaptable to automation and a cassette-based fluid-handling system (Modular Lab Pharm Tracer) has been customized for clinical radiopharmaceutical production. Our findings demonstrate that the Pb-203/Pb-212 combination is a promising elementally-matched radionuclide pair for image-gu...Continue Reading

Citations

Jan 4, 2019·European Journal of Nuclear Medicine and Molecular Imaging·José Carlos Dos SantosClemens Kratochwil
Jan 12, 2021·Journal of Controlled Release : Official Journal of the Controlled Release Society·Albert R MuslimovAlexander S Timin
Feb 3, 2021·EJNMMI Radiopharmacy and Chemistry·Brooke L McNeilPaul Schaffer
Dec 10, 2020·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Wolfgang A WeberH William Strauss
Jul 3, 2021·Pharmaceutics·Romain EychenneJean-François Gestin
Jul 29, 2020·Current Medicinal Chemistry·Mengshi LiMichael K Schultz

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