Journal article
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, Vol.127(C), pp.52-60
09/2017
DOI: 10.1016/j.apradiso.2017.05.006
PMCID: PMC6295910
PMID: 28521118
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-guided radionuclide therapy for melanoma, neuroendocrine tumors, and potentially other cancers.
•Pre-concentration of Pb-203 and Pb-212 via extraction chromatography resin was optimized for automated radiopharmaceutical production.•An HPLC isolation of Pb-203 and Pb-212 labeled peptides from unlabeled precursors produced specific activities near theoretical maximums.•The approach is robustly adaptable to automation and a cassette-based system was customized for clinical radiopharmaceutical production.
Details
- Title: Subtitle
- Automated cassette-based production of high specific activity [203/212Pb]peptide-based theranostic radiopharmaceuticals for image-guided radionuclide therapy for cancer
- Creators
- Mengshi Li - Interdisciplinary Graduate Program in Human Toxicology, University of Iowa, Iowa City, IA, USAXiuli Zhang - Department of Biochemistry, University of Missouri, Columbia, MO USAThomas P Quinn - Department of Biochemistry, University of Missouri, Columbia, MO USADongyoul Lee - Interdisciplinary Graduate Program in Human Toxicology, University of Iowa, Iowa City, IA, USADijie Liu - Stead Family Department of Pediatrics, University of Iowa, Iowa City, IA, USAFalk Kunkel - Eckert & Ziegler Radiopharma GmbH, Berlin, GermanyBrian E Zimmerman - National Institute of Standards and Technology, Gaithersburg, MD, USADaniel McAlister - Eichrom Technologies, LLC, Lisle, IL, USAKeith Olewein - Lantheus Medical Imaging, North Billerica, MA, USAYusuf Menda - Department of Radiology, The University of Iowa, Iowa City, IA, USASaed Mirzadeh - Oak Ridge National Laboratory, The US Department of Energy, Oak Ridge, TN, USARoy Copping - Oak Ridge National Laboratory, The US Department of Energy, Oak Ridge, TN, USAFrances L Johnson - Viewpoint Molecular Targeting, LLC, Coralville, IA, USAMichael K Schultz - Interdisciplinary Graduate Program in Human Toxicology, University of Iowa, Iowa City, IA, USA
- Resource Type
- Journal article
- Publication Details
- Applied radiation and isotopes, Vol.127(C), pp.52-60
- DOI
- 10.1016/j.apradiso.2017.05.006
- PMID
- 28521118
- PMCID
- PMC6295910
- NLM abbreviation
- Appl Radiat Isot
- ISSN
- 0969-8043
- eISSN
- 1872-9800
- Publisher
- Elsevier Ltd
- Language
- English
- Date published
- 09/2017
- Academic Unit
- Radiology; Stead Family Department of Pediatrics; Radiation Oncology; Internal Medicine
- Record Identifier
- 9984047986702771
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