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IFN? PET Imaging as a Predictive Tool for Monitoring Response to Tumor Immunotherapy.

ABSTRACT: IFN? is an attractive target for imaging active antitumor immunity due to its function in the T-cell signaling axis. Here, we test an IFN? immuno-PET (immunoPET) probe for its capacity to identify adaptive immunotherapy response after HER2/neu vaccination in both spontaneous salivary and orthotopic neu+ mouse mammary tumors. IFN? immunoPET detected elevated cytokine levels in situ after vaccination, which inversely correlated with tumor growth rate, an indicator of response to therapy. In a model of induced T-cell anergy where CD8 T cells infiltrate the tumor, but upregulate PD-1, IFN? tracer uptake was equivalent to isotype control, illustrating a lack of antitumor T-cell activity. The IFN? immunoPET tracer detected IFN? protein sequestered on the surface of tumor cells, likely in complex with the IFN? receptor, which may explain imaging localization of this soluble factor in vivo Collectively, we find that the activation status of cytotoxic T cells is annotated by IFN? immunoPET, with reduced off-target binding to secondary lymphoid tissues compared with imaging total CD3+ tumor-infiltrating lymphocytes. Targeting of soluble cytokines such as IFN? by PET imaging may provide valuable noninvasive insight into the function of immune cells in situ Significance: This study presents a novel approach to monitor therapeutic outcomes via IFN?-targeted positron emission tomography. Cancer Res; 78(19); 5706-17. ©2018 AACR.

SUBMITTER: Gibson HM

PROVIDER: S-EPMC6443251 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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IFNγ PET Imaging as a Predictive Tool for Monitoring Response to Tumor Immunotherapy.

Gibson Heather M HM McKnight Brooke N BN Malysa Agnes A Dyson Greg G Wiesend Wendy N WN McCarthy Claire E CE Reyes Joyce J Wei Wei-Zen WZ Viola-Villegas Nerissa T NT

Cancer research 20180816 19

IFNγ is an attractive target for imaging active antitumor immunity due to its function in the T-cell signaling axis. Here, we test an IFNγ immuno-PET (immunoPET) probe for its capacity to identify adaptive immunotherapy response after HER2/neu vaccination in both spontaneous salivary and orthotopic neu<sup>+</sup> mouse mammary tumors. IFNγ immunoPET detected elevated cytokine levels <i>in situ</i> after vaccination, which inversely correlated with tumor growth rate, an indicator of response to ...[more]

PMID: 30115693

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Project description:PurposeTumor voxel dose-response matrix (DRM) can be quantified using feedback from serial FDG-PET/CT imaging acquired during radiotherapy. This study investigated the dynamic characteristics and the predictive capability of DRM.MethodsFDG-PET/CT images were acquired before and weekly during standard chemoradiotherapy with the treatment dose 2 Gy × 35 from 31 head and neck cancer patients. For each patient, deformable image registration was performed between the pretreatment/baseline PET/CT image and each weekly PET/CT image. Tumor voxel DRM was derived using linear regression on the logarithm of the weekly standard uptake value (SUV) ratios for each tumor voxel, such as SUV measured at a dose level normalized to the baseline SUV0. The dynamic characteristics were evaluated by comparing the DRMi estimated using a single feedback image acquired at the ith treatment week (i = 1, 2, 3, or 4) to the DRM estimated using the last feedback image for each patient. The predictive capability of the DRM estimated using 1 or 2 feedback images was evaluated using the receiver operating characteristic test with respect to the treatment outcome of tumor local-regional control or failure.ResultsThe mean ± SD of tumor voxel SUV measured at the pretreatment and the 1st, 2nd, 3rd, 4th, and last treatment weeks was 6.76 ± 3.69, 5.72 ± 3.43, 3.85 ± 2.22, 3.27 ± 2.25, 2.5 ± 1.79, and 2.23 ± 1.27, respectively. The deviations between the DRMi estimated using the single feedback image obtained at the ith week and the last feedback image were 0.86 ± 4.87, -0.06 ± 0.3, -0.09 ± 0.17, and -0.09 ± 0.12 for DRM1, DRM2, DRM3, and DRM4, respectively. The predictive capability of DRM3 and DRM4 was significant (p < 0.001). The area under the curve (AUC) was increased with the increase in treatment dose level. The DRMs constructed using the single feedback image achieved an AUC of 0.86~1. The AUC was slightly improved to 0.94~1 for the DRMs estimated using 2 feedback images.ConclusionTumor voxel metabolic activity measured using FDG-PET/CT fluctuated noticeably during the first 2 treatment weeks and obtained a stabilized reduction rate thereafter. Tumor voxel DRM constructed using a single FDG-PET/CT feedback image after the 2nd treatment week (>20 Gy) has a good predictive capability. The predictive capability improved continuously using a later feedback image and marginally improved when two feedback images were applied.

Dataset Information

IFN? PET Imaging as a Predictive Tool for Monitoring Response to Tumor Immunotherapy.

Publications

IFNγ PET Imaging as a Predictive Tool for Monitoring Response to Tumor Immunotherapy.

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