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

作者：Li Mengshi; Zhang Xiuli; Quinn Thomas P; Lee Dongyoul; Liu Dijie; Kunkel Falk; Zimmerman Brian E; McAlister Daniel; Olewein Keith; Menda Yusuf; Mirzadeh Saed; Copping Roy; Johnson Frances L; Schultz Michael K^*

来源：Applied Radiation and Isotopes, 2017, 127: 52-60.

DOI：10.1016/j.apradiso.2017.05.006

• Radionuclides
• Pb-203
• Pb-212
• Alpha particle therapy
• Peptides
• Radiopharmaceuticals

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 degrees C (45 min; 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-guided radionuclide therapy for melanoma, neuroendocrine tumors, and potentially other cancers.

• 出版日期2017-9