Automated cassette-based production of high specific activity [203/212Pb]peptide-based theranostic radiopharmaceuticals for image-guided radionuclide therapy for cancer
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 (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.
- Authors:
-
- Univ. of Iowa, Iowa City, IA (United States). Interdisciplinary Graduate Program in Human Toxicology
- Univ. of Missouri, Columbia, MO (United States). Dept. of Biochemistry
- Univ. of Iowa, Iowa City, IA (United States). Stead Family Dept. of Pediatrics
- Eckert & Ziegler Radiopharma GmbH, Berlin (Germany)
- National Inst. of Standards and Technology (NIST), Gaithersburg, MD (United States)
- Eichrom Technologies, LLC, Lisle, IL (United States)
- Lantheus Medical Imaging North Billerica, MA (United States)
- Univ. of Iowa, Iowa City, IA (United States). Dept. of Radiology
- Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
- Viewpoint Molecular Targeting, LLC, Coralville, IA (United States); Univ. of Iowa, Iowa City, IA (United States). Carver College of Medicine, Dept. of Internal Medicine
- Univ. of Iowa, Iowa City, IA (United States). Interdisciplinary Graduate Program in Human Toxicology; Univ. of Iowa, Iowa City, IA (United States). Stead Family Dept. of Pediatrics; Univ. of Iowa, Iowa City, IA (United States). Dept. of Radiology; Viewpoint Molecular Targeting, LLC, Coralville, IA (United States); Univ. of Iowa, Iowa City, IA (United States). Carver College of Medicine, Dept. of Radiation Oncology; Univ. of Iowa, Iowa City, IA (United States). Dept. of Chemistry
- Publication Date:
- Research Org.:
- Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)
- Sponsoring Org.:
- USDOE
- OSTI Identifier:
- 1491308
- Grant/Contract Number:
- AC05-00OR22725
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Applied Radiation and Isotopes
- Additional Journal Information:
- Journal Volume: 127; Journal Issue: C; Journal ID: ISSN 0969-8043
- Publisher:
- Elsevier
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; Radionuclides; Pb-203; Pb-212; Alpha particle therapy; Peptides; Radiopharmaceuticals
Citation Formats
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., and Schultz, Michael K. Automated cassette-based production of high specific activity [203/212Pb]peptide-based theranostic radiopharmaceuticals for image-guided radionuclide therapy for cancer. United States: N. p., 2017.
Web. doi:10.1016/j.apradiso.2017.05.006.
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. Automated cassette-based production of high specific activity [203/212Pb]peptide-based theranostic radiopharmaceuticals for image-guided radionuclide therapy for cancer. United States. https://doi.org/10.1016/j.apradiso.2017.05.006
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., and Schultz, Michael K. Wed .
"Automated cassette-based production of high specific activity [203/212Pb]peptide-based theranostic radiopharmaceuticals for image-guided radionuclide therapy for cancer". United States. https://doi.org/10.1016/j.apradiso.2017.05.006. https://www.osti.gov/servlets/purl/1491308.
@article{osti_1491308,
title = {Automated cassette-based production of high specific activity [203/212Pb]peptide-based theranostic radiopharmaceuticals for image-guided radionuclide therapy for cancer},
author = {Li, Mengshi and Zhang, Xiuli and Quinn, Thomas P. and Lee, Dongyoul and Liu, Dijie and Kunkel, Falk and Zimmerman, Brian E. and McAlister, Daniel and Olewein, Keith and Menda, Yusuf and Mirzadeh, Saed and Copping, Roy and Johnson, Frances L. and Schultz, Michael K.},
abstractNote = {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 (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.},
doi = {10.1016/j.apradiso.2017.05.006},
journal = {Applied Radiation and Isotopes},
number = C,
volume = 127,
place = {United States},
year = {Wed May 10 00:00:00 EDT 2017},
month = {Wed May 10 00:00:00 EDT 2017}
}
Web of Science
Figures / Tables:
Works referenced in this record:
Methodology for labeling proteins and peptides with lead-212 (212Pb)
journal, July 2013
- Baidoo, Kwamena E.; Milenic, Diane E.; Brechbiel, Martin W.
- Nuclear Medicine and Biology, Vol. 40, Issue 5
From the inside out: radionuclide radiation therapy
journal, June 2016
- Bartlett, Marissa
- Australasian Physical & Engineering Sciences in Medicine, Vol. 39, Issue 2
The Potential and Hurdles of Targeted Alpha Therapy – Clinical Trials and Beyond
journal, January 2014
- Elgqvist, Jörgen; Frost, Sofia; Pouget, Jean-Pierre
- Frontiers in Oncology, Vol. 3
Nomenclature for radioanalytical chemistry (IUPAC Recommendations 1994)
journal, January 1994
- van Grieken, R.; de Bruin, M.
- Pure and Applied Chemistry, Vol. 66, Issue 12
Time-integrated activity coefficient estimation for radionuclide therapy using PET and a pharmacokinetic model: A simulation study on the effect of sampling schedule and noise: Time-integrated activity coefficient estimation for radionuclide therapy
journal, August 2016
- Hardiansyah, Deni; Guo, Wei; Kletting, Peter
- Medical Physics, Vol. 43, Issue 9
Cytotoxicity of α-particle-emitting astatine-211-labelled antibody in tumour spheroids: no effect of hyperthermia
journal, March 1998
- Hauck, Ml; Larsen, Rh; Welsh, Pc
- British Journal of Cancer, Vol. 77, Issue 5
Redefining Relative Biological Effectiveness in the Context of the EQDX Formalism: Implications for Alpha-Particle Emitter Therapy
journal, January 2014
- Hobbs, Robert F.; Howell, Roger W.; Song, Hong
- Radiation Research, Vol. 181, Issue 1
A Novel Strontium-Selective Extraction Chromatographic Resin*
journal, April 1992
- Philip Horwitz, E.; Chiarizia, Renato; Dietz, Mark L.
- Solvent Extraction and Ion Exchange, Vol. 10, Issue 2
A lead-selective extraction chromatographic resin and its application to the isolation of lead from geological samples
journal, July 1994
- Philip Horwitz, E.; Dietz, Mark L.; Rhoads, Susan
- Analytica Chimica Acta, Vol. 292, Issue 3
A Model of Cell Inactivation by Alpha-Particle Internal Emitters
journal, May 1993
- Humm, J. L.; Chin, L. M.
- Radiation Research, Vol. 134, Issue 2
Bone-Targeted Imaging and Radionuclide Therapy in Prostate Cancer
journal, October 2016
- Iagaru, Andrei H.; Mittra, Erik; Colletti, Patrick M.
- Journal of Nuclear Medicine, Vol. 57, Issue Supplement 3
α V β 3 Integrin-Targeted Radionuclide Therapy with 64 Cu-cyclam-RAFT-c(-RGDfK-) 4
journal, July 2016
- Jin, Zhao-Hui; Furukawa, Takako; Degardin, Mélissa
- Molecular Cancer Therapeutics, Vol. 15, Issue 9
Targeted α particle immunotherapy for myeloid leukemia
journal, August 2002
- Jurcic, Joseph G.; Larson, Steven M.; Sgouros, George
- Blood, Vol. 100, Issue 4
An overview of targeted alpha therapy
journal, December 2011
- Kim, Young-Seung; Brechbiel, Martin W.
- Tumor Biology, Vol. 33, Issue 3
213Bi-DOTATOC receptor-targeted alpha-radionuclide therapy induces remission in neuroendocrine tumours refractory to beta radiation: a first-in-human experience
journal, July 2014
- Kratochwil, C.; Giesel, F. L.; Bruchertseifer, F.
- European Journal of Nuclear Medicine and Molecular Imaging, Vol. 41, Issue 11
PSMA-Targeted Radionuclide Therapy of Metastatic Castration-Resistant Prostate Cancer with 177 Lu-Labeled PSMA-617
journal, March 2016
- Kratochwil, Clemens; Giesel, Frederik L.; Stefanova, Melsa
- Journal of Nuclear Medicine, Vol. 57, Issue 8
Peptide Receptor Radionuclide Therapy in the Treatment of Neuroendocrine Tumors
journal, February 2016
- Kwekkeboom, Dik J.; Krenning, Eric P.
- Hematology/Oncology Clinics of North America, Vol. 30, Issue 1
Radionuclide therapy using 131I-labeled anti-epidermal growth factor receptor-targeted nanoparticles suppresses cancer cell growth caused by EGFR overexpression
journal, November 2015
- Li, Wei; Liu, Zhongyun; Li, Chengxia
- Journal of Cancer Research and Clinical Oncology, Vol. 142, Issue 3
Peptide receptor radionuclide therapy: focus on bronchial neuroendocrine tumors
journal, July 2016
- Lo Russo, Giuseppe; Pusceddu, Sara; Prinzi, Natalie
- Tumor Biology, Vol. 37, Issue 10
Radioimmunotherapy with alpha-particle-emitting immunoconjugates
journal, May 1988
- Macklis, R.; Kinsey, B.; Kassis, A.
- Science, Vol. 240, Issue 4855
“Click”-Cyclized 68Ga-Labeled Peptides for Molecular Imaging and Therapy: Synthesis and Preliminary In Vitro and In Vivo Evaluation in a Melanoma Model System
book, August 2012
- Martin, Molly E.; Sue O’Dorisio, M.; Leverich, Whitney M.
- Theranostics, Gallium-68, and Other Radionuclides. Recent Results in Cancer Research
Radioimmunotherapy with alpha-emitting nuclides
journal, September 1998
- McDevitt, Michael R.; Sgouros, George; Finn, Ronald D.
- European Journal of Nuclear Medicine and Molecular Imaging, Vol. 25, Issue 9
203 Pb-Labeled α-Melanocyte–Stimulating Hormone Peptide as an Imaging Probe for Melanoma Detection
journal, April 2008
- Miao, Yubin; Figueroa, Said D.; Fisher, Darrell R.
- Journal of Nuclear Medicine, Vol. 49, Issue 5
Melanoma Therapy via Peptide-Targeted -Radiation
journal, August 2005
- Miao, Y.
- Clinical Cancer Research, Vol. 11, Issue 15
Peptide-targeted radionuclide therapy for melanoma
journal, September 2008
- Miao, Yubin; Quinn, Thomas P.
- Critical Reviews in Oncology/Hematology, Vol. 67, Issue 3
Potentiation of Peptide Receptor Radionuclide Therapy by the PARP Inhibitor Olaparib
journal, January 2016
- Nonnekens, Julie; van Kranenburg, Melissa; Beerens, Cecile E. M. T.
- Theranostics, Vol. 6, Issue 11
Targeted Radionuclide Therapy of Melanoma
journal, May 2016
- Norain, Abdullah; Dadachova, Ekaterina
- Seminars in Nuclear Medicine, Vol. 46, Issue 3
Alpha-particles for targeted therapy
journal, September 2008
- Sgouros, George
- Advanced Drug Delivery Reviews, Vol. 60, Issue 12
Modelling and Dosimetry for Alpha-Particle Therapy
journal, July 2011
- Sgouros, George; F. Hobbs, Robert; Song, Hong
- Current Radiopharmaceuticalse, Vol. 4, Issue 3
MIRD Pamphlet No. 22 (Abridged): Radiobiology and Dosimetry of -Particle Emitters for Targeted Radionuclide Therapy
journal, January 2010
- Sgouros, G.; Roeske, J. C.; McDevitt, M. R.
- Journal of Nuclear Medicine, Vol. 51, Issue 2
Cancer Stem Cell Targeting Using the Alpha-Particle Emitter, 213 Bi: Mathematical Modeling and Feasibility Analysis
journal, February 2008
- Sgouros, George; Song, Hong
- Cancer Biotherapy and Radiopharmaceuticals, Vol. 23, Issue 1
A Monte Carlo study on 223 Ra imaging for unsealed radionuclide therapy: Monte Carlo study on 223 Ra imaging
journal, May 2016
- Takahashi, Akihiko; Miwa, Kenta; Sasaki, Masayuki
- Medical Physics, Vol. 43, Issue 6Part1
Molecular Targeted α-Particle Therapy for Oncologic Applications
journal, August 2014
- Wadas, Thaddeus J.; Pandya, Darpan N.; Solingapuram Sai, Kiran Kumar
- American Journal of Roentgenology, Vol. 203, Issue 2
Molecular Imaging and Targeted Radionuclide Therapy of Prostate Cancer
journal, October 2016
- Weber, Wolfgang A.; Morris, Michael J.
- Journal of Nuclear Medicine, Vol. 57, Issue Supplement 3
Works referencing / citing this record:
Development and dosimetry of 203Pb/212Pb-labelled PSMA ligands: bringing “the lead” into PSMA-targeted alpha therapy?
journal, January 2019
- dos Santos, José Carlos; Schäfer, Martin; Bauder-Wüst, Ulrike
- European Journal of Nuclear Medicine and Molecular Imaging, Vol. 46, Issue 5
Figures / Tables found in this record: