Can 89Zr-atezolizumab PET scan identify patients with metastatic invasive lobular breast cancer who will respond to chemotherapy-immune checkpoint inhibition? - ImaGelato study

Start Date18 Dec 2019

Sponsor / Collaborator

Universitair Medisch Centrum Groningen

NCT04006522 / RecruitingPhase 2IIT

An Exploratory Study of 89Zr-DFO-Atezolizumab ImmunoPET/CT in Patients With Locally Advanced or Metastatic Renal Cell Carcinoma

This is an exploratory clinical trial to assess the potential of 89Zr-DFO-Atezolizumab Positron Emission Tomography/Computed Tomography (PET/CT) scans in patients with locally advanced or metastatic renal cell carcinoma (RCC). This open label, nontherapeutic trial will test the correlation of 89Zr-DFO-Atezolizumab immunoPET/CT with programmed death-ligand 1 (PD-L1) expression and the response to immune checkpoint inhibitor therapy in patients with RCC. There will be two cohorts, one made up of patients with localized RCC who will undergo 89Zr-DFO-Atezolizumab PET/CT prior to nephrectomy and a second cohort of patients with metastatic RCC who will undergo 89Zr-DFO-Atezolizumab PET/CT prior to treatment with an immune checkpoint inhibitor.

Start Date02 Oct 2019

Sponsor / Collaborator

The University of Texas Southwestern Medical Center

EUCTR2019-001197-28-NL / Not yet recruitingPhase 2

Can 89Zr-atezolizumab PET scan identify patients with metastatic invasive lobular breast cancer who will respond to chemotherapy-immune checkpoint inhibition? - ImaGelato

Start Date31 Jul 2019

Sponsor / Collaborator

University Medical Center Groningen

100 Clinical Results associated with 89Zr-DFO-Atezolizumab

100 Translational Medicine associated with 89Zr-DFO-Atezolizumab

100 Patents (Medical) associated with 89Zr-DFO-Atezolizumab

Literatures (Medical) associated with 89Zr-DFO-Atezolizumab

14 Nov 2022·Clinical cancer research : an official journal of the American Association for Cancer Research

ImmunoPET Imaging with 89Zr-Labeled Atezolizumab Enables In Vivo Evaluation of PD-L1 in Tumorgraft Models of Renal Cell Carcinoma

Article

Author: Brugarolas, James ; Stevens, Christina ; Nham, Kien ; Bowman, I. Alex ; Guan, Bing ; Tcheuyap, Vanina T. ; Elias, Roy ; Singla, Nirmish ; Hao, Guiyang ; Mulgaonkar, Aditi ; Kapur, Payal ; Woolford, Layton ; Sun, Xiankai ; Christie, Alana

Abstract:

Purpose::

Immune checkpoint inhibitors (ICI) targeting the programmed cell death protein 1 and its ligand (PD-1/PD-L1) have transformed the treatment paradigm for metastatic renal cell carcinoma (RCC). However, response rates to ICIs as single agents or in combination vary widely and predictive biomarkers are lacking. Possibly related to the heterogeneity and dynamic nature of PD-L1 expression, tissue-based methods have shown limited value. Immuno–positron emission tomography (immunoPET) may enable noninvasive, comprehensive, and real-time PD-L1 detection. Herein, we systematically examined the performance of immunoPET for PD-L1 detection relative to IHC in an RCC patient-derived tumorgraft (TG) platform.

Experimental Design::

Eight independent RCC TGs with a wide range of PD-L1 expression (0%–85%) were evaluated by immunoPET. Uptake of 89Zr-labeled atezolizumab ([89Zr]Zr-DFO-ATZ) was compared with PD-L1 expression in tumors by IHC through double-blind analyses. Clinical outcomes of ICI-treated patients whose TGs were examined were analyzed to evaluate the clinical role of immunoPET in RCC.

Results::

ImmunoPET with [89Zr]Zr-DFO-ATZ (day 6/7 postinjection) revealed a statistically significant association with PD-L1 IHC assays (P = 0.0014; correlation ρXY = 0.78). Furthermore, immunoPET can be used to assess the heterogeneous distribution of PD-L1 expression. Finally, studies in the corresponding patients (n = 4) suggest that PD-L1 signal may influence ICI responsiveness.

Conclusions::

ImmunoPET with [89Zr]Zr-DFO-ATZ may enable a thorough and dynamic assessment of PD-L1 across sites of disease. The power of immunoPET to predict ICI response in RCC is being explored in an ongoing clinical trial (NCT04006522).

01 Sep 2021·Nuclear medicine and biologyQ4 · MEDICINE

Non-invasive immunoPET imaging of PD-L1 using anti-PD-L1-B11 in breast cancer and melanoma tumor model

Q4 · MEDICINE

Article

Author: Pandey, Mukesh K ; Bansal, Aditya ; Lucien, Fabrice ; Park, Sean S ; Liu, Xin ; Harrington, Susan M ; Barham, Whitney ; Dong, Haidong ; DeGrado, Timothy R

INTRODUCTION:

Immunotherapy targeting PD-1/PD-L1 immune checkpoint inhibition (ICI) is efficacious in various solid and hematologic malignancies. However, the response rate to PD-1/PD-L1 therapy is only 15-35%. To obtain optimal clinical response to ICI therapies, a reliable assessment of tumor PD-L1 expression is needed to select appropriate patients, and a non-invasive imaging-based assessment of PD-L1 expression is critically needed. Although radiolabeled PET probes based on PD-L1 targeted therapeutic antibodies (e.g. atezolizumab) have shown encouraging results, there is concern that residual therapeutic antibody may compete for binding with the radiotracer thereby compromising imaging studies that follow treatment.

METHODS AND RESULTS:

In this study, we used novel anti-PD-L1-B11 clone antibody known to bind to a different epitope of PD-L1 than the therapeutic antibodies to avoid potential saturation effects. The anti-PD-L1-B11 clone was radiolabeled with zirconium-89 and evaluated to detect PD-L1 expression in various in vitro and in vivo cancer model systems in comparison with [⁸⁹Zr]Zr-DFO-NCS-atezolizumab. In vitro binding parameters of anti-PD-L1-B11 were like those of atezolizumab. [⁸⁹Zr]Zr-DFO-NCS-anti-PD-L1-B11 clone showed favorable properties to [⁸⁹Zr]Zr-DFO-NCS-atezolizumab in an in vivo breast cancer tumor model system with higher uptake in PD-L1 expressing tumors.

CONCLUSION:

Our data demonstrates that [⁸⁹Zr]Zr-DFO-NCS-anti-PD-L1-B11 exhibits excellent imaging properties for the assessment PD-L1 expression. The independent binding site of anti-PD-L1-B11 relative to therapeutic anti-PD-L1 antibodies may be advantageous for anti-PD-L1 therapy monitoring.

15 Feb 2021·Clinical cancer research : an official journal of the American Association for Cancer ResearchQ1 · MEDICINE

Molecular Imaging of Chimeric Antigen Receptor T Cells by ICOS-ImmunoPET

Q1 · MEDICINE

Article

Author: Miklos, David B. ; Malipatlolla, Meena B. ; Sathirachinda, Ataya ; Schultz, Liora M. ; Lohmeyer, Juliane K. ; Xiao, Zunyu ; Robinson, Elise ; Vermesh, Ophir ; Gambhir, Sanjiv S. ; Mackall, Crystal L. ; Scheller, Lukas ; Sahaf, Bita ; Spiegel, Jay Y. ; Lee, Jason T. ; Hirai, Toshihito ; Negrin, Robert S. ; Alam, Israt S. ; Engels, Pujan ; Good, Zinaida ; Baker, Jeanette ; Haywood, Tom ; Chen, Weiyu ; Simonetta, Federico

Abstract:

Purpose::

Immunomonitoring of chimeric antigen receptor (CAR) T cells relies primarily on their quantification in the peripheral blood, which inadequately quantifies their biodistribution and activation status in the tissues. Noninvasive molecular imaging of CAR T cells by PET is a promising approach with the ability to provide spatial, temporal, and functional information. Reported strategies rely on the incorporation of reporter transgenes or ex vivo biolabeling, significantly limiting the application of CAR T-cell molecular imaging. In this study, we assessed the ability of antibody-based PET (immunoPET) to noninvasively visualize CAR T cells.

Experimental Design::

After analyzing human CAR T cells in vitro and ex vivo from patient samples to identify candidate targets for immunoPET, we employed a syngeneic, orthotopic murine tumor model of lymphoma to assess the feasibility of in vivo tracking of CAR T cells by immunoPET using the 89Zr-DFO-anti-ICOS tracer, which we have previously reported.

Results::

Analysis of human CD19-CAR T cells during activation identified the Inducible T-cell COStimulator (ICOS) as a potential target for immunoPET. In a preclinical tumor model, 89Zr-DFO-ICOS mAb PET-CT imaging detected significantly higher signal in specific bone marrow–containing skeletal sites of CAR T-cell–treated mice compared with controls. Importantly, administration of ICOS-targeting antibodies at tracer doses did not interfere with CAR T-cell persistence and function.

Conclusions::

This study highlights the potential of ICOS-immunoPET imaging for monitoring of CAR T-cell therapy, a strategy readily applicable to both commercially available and investigational CAR T cells.See related commentary by Volpe et al., p. 911

100 Deals associated with 89Zr-DFO-Atezolizumab

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Indication	Highest Phase	Country/Location	Organization	Date
Locally Advanced Renal Cell Carcinoma	Phase 2	US	The University of Texas Southwestern Medical Center	02 Oct 2019

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