2017
DOI: 10.1021/acs.bioconjchem.7b00631
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Abstract: High sensitivity imaging tools could provide a more holistic view of target antigen expression to improve the identification of patients who might benefit from cancer immunotherapy. We developed for immunoPET a novel recombinant human IgG1 (termed C4) that potently binds an extracellular epitope on human and mouse PD-L1 and radiolabeled the antibody with zirconium-89. Small animal PET/CT studies showed that 89Zr-C4 detected antigen levels on a patient derived xenograft (PDX) established from a non-small-cell l… Show more

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Cited by 112 publications
(79 citation statements)
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“…To compare the biodistribution of anti-CTLA4 and anti-CTLA4 DVD in vivo, the Abs were conjugated to the chelator desferrioxamine B (DFO) via solvent-exposed ε amino groups on lysine side chains. The DFO-conjugated Abs were coupled to 89 Zr using previously reported conditions (16). Evaluating the biodistribution of 89 Zr-anti-CTLA4 in intact male C57BL6/j mice with s.c. TRAMP-C2 injection by PET/CT showed that the radiotracer accumulated in the tumor over 8 to 72 hours, while the radiotracer retention in the blood generally declined over 8 to 72 hours, as expected (Supplemental Figure 3).…”
Section: Resultsmentioning
confidence: 99%
“…To compare the biodistribution of anti-CTLA4 and anti-CTLA4 DVD in vivo, the Abs were conjugated to the chelator desferrioxamine B (DFO) via solvent-exposed ε amino groups on lysine side chains. The DFO-conjugated Abs were coupled to 89 Zr using previously reported conditions (16). Evaluating the biodistribution of 89 Zr-anti-CTLA4 in intact male C57BL6/j mice with s.c. TRAMP-C2 injection by PET/CT showed that the radiotracer accumulated in the tumor over 8 to 72 hours, while the radiotracer retention in the blood generally declined over 8 to 72 hours, as expected (Supplemental Figure 3).…”
Section: Resultsmentioning
confidence: 99%
“…A 89 Zr-labeled mAb against mouse PD-L1 was used to show increased tracer uptake in a syngeneic head and neck tumor model after fractionated radiotherapy (Kikuchi et al 2017). Other research teams have also successfully employed mAbs for imaging of PD-L1 using different radionuclides, including 89 Zr, 111 In, 64 Cu and 131 I (Hettich et al 2016;Chatterjee et al 2016;Josefsson et al 2016;Nedrow et al 2017aNedrow et al , 2017bLesniak et al 2016;Li et al 2018;Moroz et al 2018;Truillet et al 2018;Pang et al 2018).…”
Section: Pd-l1 Imagingmentioning
confidence: 99%
“…Preclinical studies showed that immuno‐PET monitoring of CD8+ T cells could serve as a predictive and prognostic biomarker for immune checkpoint therapy . Currently, effective efforts are underway to define PD‐L1 or PD‐1 expression using noninvasive molecular probes, of which a large number of studies focused on the feasibility of antibody‐based tracers in immunotherapy …”
Section: Imaging Biomarkers For Immune Checkpoint Therapymentioning
confidence: 99%
“…71,72 Currently, effective efforts are underway to define PD-L1 or PD-1 expression using noninvasive molecular probes, of which a large number of studies focused on the feasibility of antibody-based tracers in immunotherapy. [73][74][75][76][77][78][79][80][81][82] For PET/CT-based molecular imaging, 64 Cu and 89 Zr are the most common radionuclides used in immuno-oncology. HTXM-MST 64 Cu-, 89 Zr-labeled antibodies 74,77,79 PD-L1 expression -HTXM-MST 89 Zr-, 64 Cu-labeled antibodies 81,82 PD-1 expression -HTXM-MST 89 Zr-labeled antibody 83 TR; PFS, OS…”
Section: Molecular Imagingmentioning
confidence: 99%