A Preclinical Assessment of 89 Zr-atezolizumab Identifies a Requirement for Carrier Added Formulations Not Observed with 89 Zr-C4

Bioconjugate Chemistry
Anna MorozMichael J Evans

Abstract

The swell of experimental imaging technologies to noninvasively measure immune checkpoint protein expression presents the opportunity for rigorous comparative studies toward identifying a gold standard. 89Zr-atezolizumab is currently in man, and early data show tumor targeting but also abundant uptake in several normal tissues. Therefore, we conducted a reverse translational study both to understand if tumor to normal tissue ratios for 89Zr-atezolizumab could be improved and to make direct comparisons to 89Zr-C4, a radiotracer that we showed can detect a large dynamic range of tumor-associated PD-L1 expression. PET/CT and biodistribution studies in tumor bearing immunocompetent and nu/nu mice revealed that high specific activity 89Zr-atezolizumab (∼2 μCi/μg) binds to PD-L1 on tumors but also results in very high uptake in many normal mouse tissues, as expected. Unexpectedly, 89Zr-atezolizumab uptake was generally higher in normal mouse tissues compared to 89Zr-C4 and lower in H1975, a tumor model with modest PD-L1 expression. Also unexpectedly, reducing the specific activity at least 15-fold suppressed 89Zr-atezo uptake in normal mouse tissues but increased tumor uptake to levels observed with high specific activity 89Zr-C4. In...Continue Reading

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Citations

Aug 20, 2020·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Junnian WeiMichael J Evans
Nov 7, 2019·EJNMMI Radiopharmacy and Chemistry·Peter WierstraSandra Heskamp
Nov 20, 2019·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Lin QiuHongcheng Shi
Dec 29, 2019·European Journal of Nuclear Medicine and Molecular Imaging·Camilla ChristensenAndreas Kjaer
Jan 27, 2021·European Journal of Nuclear Medicine and Molecular Imaging·Teja Muralidhar KalidindiNaga Vara Kishore Pillarsetty
Oct 17, 2020·Cancer Management and Research·Weiqing WangXue Meng
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Dec 12, 2020·Pharmacology & Therapeutics·Alizée BouleauCharles Truillet
Jul 8, 2021·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Vasilios LiapisAlexander H Staudacher
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Sep 21, 2021·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Federica Pisaneschi, Nerissa T Viola

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