TY - JOUR
T1 - The Role of 89Zr-Immuno-PET in Navigating and Derisking the Development of Biopharmaceuticals
AU - van Dongen, Guus A. M. S.
AU - Beaino, Wissam
AU - Windhorst, Albert D.
AU - Zwezerijnen, Gerben J. C.
AU - Oprea-Lager, Daniela E.
AU - Hendrikse, N. Harry
AU - van Kuijk, Cornelis
AU - Boellaard, Ronald
AU - Huisman, Marc C.
AU - Vugts, Danielle J.
N1 - Publisher Copyright: © 2021 Society of Nuclear Medicine Inc.. All rights reserved.
PY - 2021/4/1
Y1 - 2021/4/1
N2 - The identification of molecular drivers of disease and the compelling rise of biotherapeutics have impacted clinical care but have also come with challenges. Such therapeutics include peptides, monoclonal antibodies, antibody fragments and nontraditional binding scaffolds, activatable antibodies, bispecific antibodies, immunocytokines, antibody-drug conjugates, enzymes, polynucleotides, and therapeutic cells, as well as alternative drug carriers such as nanoparticles. Drug development is expensive, attrition rates are high, and efficacy rates are lower than desired. Almost all these drugs, which in general have a long residence time in the body, can stably be 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 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 biologic drugs. Appealing showcases are discussed to illustrate what can be learned with this emerging technology during preclinical and especially clinical studies about biologic 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 on why certain drug-target combinations might have better perspectives than others.
AB - The identification of molecular drivers of disease and the compelling rise of biotherapeutics have impacted clinical care but have also come with challenges. Such therapeutics include peptides, monoclonal antibodies, antibody fragments and nontraditional binding scaffolds, activatable antibodies, bispecific antibodies, immunocytokines, antibody-drug conjugates, enzymes, polynucleotides, and therapeutic cells, as well as alternative drug carriers such as nanoparticles. Drug development is expensive, attrition rates are high, and efficacy rates are lower than desired. Almost all these drugs, which in general have a long residence time in the body, can stably be 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 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 biologic drugs. Appealing showcases are discussed to illustrate what can be learned with this emerging technology during preclinical and especially clinical studies about biologic 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 on why certain drug-target combinations might have better perspectives than others.
KW - 89Zr-immuno-PET
KW - Antibody-drug conjugates
KW - Biopharmaceuticals
KW - Immune checkpoint inhibitors
KW - Monoclonal antibodies
KW - Zr-89-immuno-PET
UR - http://www.scopus.com/inward/record.url?scp=85103682381&partnerID=8YFLogxK
U2 - https://doi.org/10.2967/jnumed.119.239558
DO - https://doi.org/10.2967/jnumed.119.239558
M3 - Article
C2 - 33277395
SN - 0161-5505
VL - 62
SP - 438
EP - 445
JO - Journal of nuclear medicine
JF - Journal of nuclear medicine
IS - 4
ER -