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
References
Apr 6, 2011·Cancer Biology & Therapy·Jeffrey N BryanMichael R Lewis
Nov 28, 2014·Nature·Roy S HerbstF Stephen Hodi
Feb 20, 2015·Molecular Cancer Therapeutics·Sandip Pravin Patel, Razelle Kurzrock
Mar 13, 2015·Radiographics : a Review Publication of the Radiological Society of North America, Inc·Jennifer J KwakHeather A Jacene
Mar 15, 2015·Science·Naiyer A RizviTimothy A Chan
Feb 6, 2016·Oncotarget·Samit ChatterjeeSridhar Nimmagadda
Jul 28, 2016·Bioconjugate Chemistry·Wojciech G LesniakSridhar Nimmagadda
Jul 30, 2016·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Emily B EhlerdingWeibo Cai
Dec 28, 2016·Biochemical and Biophysical Research Communications·Samit ChatterjeeSridhar Nimmagadda
Apr 9, 2017·European Journal of Nuclear Medicine and Molecular Imaging·Annie N M WongRodney J Hicks
Jun 10, 2017·Science·Dung T LeLuis A Diaz
Oct 14, 2017·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·David J DonnellyWendy Hayes
Nov 11, 2017·Bioconjugate Chemistry·Charles TruilletMichael J Evans
Jan 25, 2018·Cancer Research·Sai Kiran SharmaJason S Lewis
May 2, 2018·Trends in Cancer·Weijun WeiWeibo Cai
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
May 3, 2019·Molecular Imaging·Elaine M JagodaPeter L Choyke
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
Nov 4, 2020·Cancers·Sridhar Nimmagadda
Mar 9, 2019·Current Opinion in Biotechnology·Koli BasuCharles S Craik
Jun 26, 2020·International Journal of Radiation Oncology, Biology, Physics·Robert R FlavellSue S Yom
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
Apr 12, 2019·Bioconjugate Chemistry·Emily B EhlerdingWeibo Cai
Mar 24, 2020·Chemical Reviews·Weijun WeiWeibo Cai
Apr 28, 2020·ACS Omega·Jun ZhaoChun Li
Sep 21, 2021·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Federica Pisaneschi, Nerissa T Viola
Dec 16, 2021·Molecular Pharmaceutics·Hanxiang LiuLin Qiu