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OtherState-of-the-Art (Invitation Only)

The navigating and de-risking role of 89Zr-immuno-PET in the development of biopharmaceuticals

Guus A.M.S. van Dongen, Wissam Beaino, Albert D. Windhorst, Gerben J.C. Zwezerijnen, Daniela E. Oprea-Lager, N. Harry Hendrikse, Cornelis C. Van Kuijk, Ronald Boellaard, Marc C. Huisman and Danielle J Vugts
Journal of Nuclear Medicine December 2020, jnumed.119.239558; DOI: https://doi.org/10.2967/jnumed.119.239558
Guus A.M.S. van Dongen
Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Netherlands
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Wissam Beaino
Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Netherlands
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Albert D. Windhorst
Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Netherlands
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Gerben J.C. Zwezerijnen
Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Netherlands
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Daniela E. Oprea-Lager
Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Netherlands
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N. Harry Hendrikse
Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Netherlands
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Cornelis C. Van Kuijk
Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Netherlands
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Ronald Boellaard
Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Netherlands
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Marc C. Huisman
Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Netherlands
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Danielle J Vugts
Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Netherlands
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Abstract

The identification of molecular drivers of disease and the compelling rise of biotherapeutics such as peptides, monoclonal antibodies, antibody fragments and non-traditional binding scaffolds, activatable antibodies, bispecific antibodies, immunocytokines, antibody drug conjugates, enzymes, polynucleotides, therapeutic cells as well as alternative drug carriers like nanoparticles have impacted clinical care but also came with challenges. Drug development is expensive, attrition rates are high, and efficacy rates are lower than desired. Nowadays almost all these drugs, that in general have a long residence time in the body, can be stably labeled with 89Zr for whole body-PET imaging and quantification. Although not restricted to monoclonal antibodies, this approach is called 89Zr-immuno-PET. This review summarizes at a high level the State of the Art of the technical aspects of 89Zr-immuno-PET, and illustrates why it has potential for steering the design, development and application of biological drugs. Appealing showcases are discussed to illustrate what can be learned with this emerging technology during preclinical and especially clinical studies about biological drug formats and disease targets. In addition, an overview of ongoing and completed clinical trials is provided. Although 89Zr-immuno-PET is a young tool in drug development, its application is rapidly expanding, with first clinical experiences giving insight why certain drug-target combinations might have better perspectives than others.

  • Molecular Imaging
  • Monoclonal Antibodies
  • PET
  • 89Zr-immuno-PET
  • antibody-drug conjugates
  • biopharmaceuticals
  • immune checkpoint inhibitors
  • monoclonal antibodies
  • Copyright © 2020 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

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Journal of Nuclear Medicine: 62 (3)
Journal of Nuclear Medicine
Vol. 62, Issue 3
March 1, 2021
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The navigating and de-risking role of 89Zr-immuno-PET in the development of biopharmaceuticals
Guus A.M.S. van Dongen, Wissam Beaino, Albert D. Windhorst, Gerben J.C. Zwezerijnen, Daniela E. Oprea-Lager, N. Harry Hendrikse, Cornelis C. Van Kuijk, Ronald Boellaard, Marc C. Huisman, Danielle J Vugts
Journal of Nuclear Medicine Dec 2020, jnumed.119.239558; DOI: 10.2967/jnumed.119.239558

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The navigating and de-risking role of 89Zr-immuno-PET in the development of biopharmaceuticals
Guus A.M.S. van Dongen, Wissam Beaino, Albert D. Windhorst, Gerben J.C. Zwezerijnen, Daniela E. Oprea-Lager, N. Harry Hendrikse, Cornelis C. Van Kuijk, Ronald Boellaard, Marc C. Huisman, Danielle J Vugts
Journal of Nuclear Medicine Dec 2020, jnumed.119.239558; DOI: 10.2967/jnumed.119.239558
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Keywords

  • molecular imaging
  • Monoclonal Antibodies
  • PET
  • 89Zr-immuno-PET
  • antibody-drug conjugates
  • biopharmaceuticals
  • Immune checkpoint inhibitors
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