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

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

doi:10.1016/j.apradiso.2017.05.006

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

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

Research output: Contribution to journal › Article › peer-review

36 Scopus citations

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.

Original language	English
Pages (from-to)	52-60
Number of pages	9
Journal	Applied Radiation and Isotopes
Volume	127
DOIs	https://doi.org/10.1016/j.apradiso.2017.05.006
State	Published - Sep 1 2017
Externally published	Yes

Funding

Funders	Funder number
National Cancer Institute	R43CA203430

Keywords

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.apradiso.2017.05.006

Cite this

Li, M., Zhang, X., Quinn, T. P., Lee, D., Liu, D., Kunkel, F., Zimmerman, B. E., McAlister, D., Olewein, K., Menda, Y., Mirzadeh, S., Copping, R., Johnson, F. L., & Schultz, M. K. (2017). 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, 127, 52-60. https://doi.org/10.1016/j.apradiso.2017.05.006

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title = "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.",

keywords = "Alpha particle therapy, Pb-203, Pb-212, Peptides, Radionuclides, Radiopharmaceuticals",

author = "Mengshi Li and Xiuli Zhang and Quinn, {Thomas P.} and Dongyoul Lee and Dijie Liu and Falk Kunkel and Zimmerman, {Brian E.} and Daniel McAlister and Keith Olewein and Yusuf Menda and Saed Mirzadeh and Roy Copping and Johnson, {Frances L.} and Schultz, {Michael K.}",

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doi = "10.1016/j.apradiso.2017.05.006",

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Li, M, Zhang, X, Quinn, TP, Lee, D, Liu, D, Kunkel, F, Zimmerman, BE, McAlister, D, Olewein, K, Menda, Y, Mirzadeh, S, Copping, R, Johnson, FL & Schultz, MK 2017, '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, pp. 52-60. https://doi.org/10.1016/j.apradiso.2017.05.006

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T1 - Automated cassette-based production of high specific activity [203/212Pb]peptide-based theranostic radiopharmaceuticals for image-guided radionuclide therapy for cancer

AU - Li, Mengshi

AU - Zhang, Xiuli

AU - Quinn, Thomas P.

AU - Lee, Dongyoul

AU - Liu, Dijie

AU - Kunkel, Falk

AU - Zimmerman, Brian E.

AU - McAlister, Daniel

AU - Olewein, Keith

AU - Menda, Yusuf

AU - Mirzadeh, Saed

AU - Copping, Roy

AU - Johnson, Frances L.

AU - Schultz, Michael K.

PY - 2017/9/1

Y1 - 2017/9/1

N2 - 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.

AB - 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.

KW - Alpha particle therapy

KW - Pb-203

KW - Pb-212

KW - Peptides

KW - Radionuclides

KW - Radiopharmaceuticals

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