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89 Zr-atezolizumab imaging as a non-invasive approach to assess clinical response to PD-L1 blockade in cancer.

Authors :
Bensch F
van der Veen EL
Lub-de Hooge MN
Jorritsma-Smit A
Boellaard R
Kok IC
Oosting SF
Schröder CP
Hiltermann TJN
van der Wekken AJ
Groen HJM
Kwee TC
Elias SG
Gietema JA
Bohorquez SS
de Crespigny A
Williams SP
Mancao C
Brouwers AH
Fine BM
de Vries EGE
Source :
Nature medicine [Nat Med] 2018 Dec; Vol. 24 (12), pp. 1852-1858. Date of Electronic Publication: 2018 Nov 26.
Publication Year :
2018

Abstract

Programmed cell death protein-1/ligand-1 (PD-1/PD-L1) blockade is effective in a subset of patients with several tumor types, but predicting patient benefit using approved diagnostics is inexact, as some patients with PD-L1-negative tumors also show clinical benefit <superscript>1,2</superscript> . Moreover, all biopsy-based tests are subject to the errors and limitations of invasive tissue collection <superscript>3-11</superscript> . Preclinical studies of positron-emission tomography (PET) imaging with antibodies to PD-L1 suggested that this imaging method might be an approach to selecting patients <superscript>12,13</superscript> . Such a technique, however, requires substantial clinical development and validation. Here we present the initial results from a first-in-human study to assess the feasibility of imaging with zirconium-89-labeled atezolizumab (anti-PD-L1), including biodistribution, and secondly test its potential to predict response to PD-L1 blockade (ClinicalTrials.gov identifiers NCT02453984 and NCT02478099). We imaged 22 patients across three tumor types before the start of atezolizumab therapy. The PET signal, a function of tracer exposure and target expression, was high in lymphoid tissues and at sites of inflammation. In tumors, uptake was generally high but heterogeneous, varying within and among lesions, patients, and tumor types. Intriguingly, clinical responses in our patients were better correlated with pretreatment PET signal than with immunohistochemistry- or RNA-sequencing-based predictive biomarkers, encouraging further development of molecular PET imaging for assessment of PD-L1 status and clinical response prediction.

Details

Language :
English
ISSN :
1546-170X
Volume :
24
Issue :
12
Database :
MEDLINE
Journal :
Nature medicine
Publication Type :
Academic Journal
Accession number :
30478423
Full Text :
https://doi.org/10.1038/s41591-018-0255-8