Dataset Information

Noise-Induced Variability of Immuno-PET with Zirconium-89-Labeled Antibodies: an Analysis Based on Count-Reduced Clinical Images.

ABSTRACT:

Purpose

Positron emission tomography (PET) with Zirconium-89 (Zr-89)-labeled antibodies can be used for in vivo quantification of antibody uptake. Knowledge about measurement variability is required to ensure correct interpretation. However, no clinical studies have been reported on measurement variability of Zr-89 immuno-PET. As variability due to low signal-to-noise is part of the total measurement variability, the aim of this study was to assess noise-induced variability of Zr-89 -immuno-PET using count-reduced clinical images.

Procedures

Data were acquired from three previously reported clinical studies with [⁸⁹Zr]antiCD20 (74 MBq, n = 7), [⁸⁹Zr]antiEGFR (37 MBq, n = 7), and [⁸⁹Zr]antiCD44 (37 MBq, n = 13), with imaging obtained 1 to 6 days post injection (D0-D6). Volumes of interest (VOIs) were manually delineated for liver, spleen, kidney, lung, brain, and tumor. For blood pool and bone marrow, fixed-size VOIs were used. Original PET list mode data were split and reconstructed, resulting in two count-reduced images at 50 % of the original injected dose (e.g., 37 MBq_74inj). Repeatability coefficients (RC) were obtained from Bland-Altman analysis on standardized uptake values (SUV) derived from VOIs applied to these images.

Results

The RC for the combined manually delineated organs for [⁸⁹Zr] antiCD20 (37 MBq_74inj) increased from D0 to D6 and was less than 6 % at all time points. Blood pool and bone marrow had higher RC, up to 43 % for 37 MBq_74inj at D6. For tumor, the RC was up to 42 % for [⁸⁹Zr]antiCD20 (37 MBq_74inj). For [⁸⁹Zr]antiCD20, (18 MBq_74inj), [⁸⁹Zr]antiEGFR (18 MBq_37inj), and [⁸⁹Zr]antiCD44 (18 MBq_37inj), measurement variability was independent of the investigated antibody.

Conclusions

Based on this study, noise-induced variability results in a RC for Zr-89-immuno-PET (37 MBq) around 6 % for manually delineated organs combined, increasing up to 43 % at D6 for blood pool and bone marrow, assuming similar biodistribution of antibodies. The signal-to-noise ratio leads to tumor RC up to 42 %.

SUBMITTER: Jauw YWS

PROVIDER: S-EPMC6244539 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Publications

Noise-Induced Variability of Immuno-PET with Zirconium-89-Labeled Antibodies: an Analysis Based on Count-Reduced Clinical Images.

Jauw Yvonne W S YWS Heijtel Dennis F DF Zijlstra Josée M JM Hoekstra Otto S OS de Vet Henrica C W HCW Vugts Danielle J DJ Verheul Henk M HM Boellaard Ronald R Zweegman Sonja S van Dongen Guus A M S GAMS der Houven van Oordt C Willemien Menke-van CWM Lammertsma Adriaan A AA Huisman Marc C MC

Molecular imaging and biology 20181201 6

<h4>Purpose</h4>Positron emission tomography (PET) with Zirconium-89 (Zr-89)-labeled antibodies can be used for in vivo quantification of antibody uptake. Knowledge about measurement variability is required to ensure correct interpretation. However, no clinical studies have been reported on measurement variability of Zr-89 immuno-PET. As variability due to low signal-to-noise is part of the total measurement variability, the aim of this study was to assess noise-induced variability of Zr-89 -imm ...[more]

PMID: 29713958

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Project description:Selection of the right drug for the right patient is a promising approach to increase clinical benefit of targeted therapy with monoclonal antibodies (mAbs). Assessment of in vivo biodistribution and tumor targeting of mAbs to predict toxicity and efficacy is expected to guide individualized treatment and drug development. Molecular imaging with positron emission tomography (PET) using zirconium-89 ((89)Zr)-labeled monoclonal antibodies also known as (89)Zr-immuno-PET, visualizes and quantifies uptake of radiolabeled mAbs. This technique provides a potential imaging biomarker to assess target expression, as well as tumor targeting of mAbs. In this review we summarize results from initial clinical trials with (89)Zr-immuno-PET in oncology and discuss technical aspects of trial design. In clinical trials with (89)Zr-immuno-PET two requirements should be met for each (89)Zr-labeled mAb to realize its full potential. One requirement is that the biodistribution of the (89)Zr-labeled mAb (imaging dose) reflects the biodistribution of the drug during treatment (therapeutic dose). Another requirement is that tumor uptake of (89)Zr-mAb on PET is primarily driven by specific, antigen-mediated, tumor targeting. Initial trials have contributed toward the development of (89)Zr-immuno-PET as an imaging biomarker by showing correlation between uptake of (89)Zr-labeled mAbs on PET and target expression levels in biopsies. These results indicate that (89)Zr-immuno-PET reflects specific, antigen-mediated binding. (89)Zr-immuno-PET was shown to predict toxicity of RIT, but thus far results indicating that toxicity of mAbs or mAb-drug conjugate treatment can be predicted are lacking. So far, one study has shown that molecular imaging combined with early response assessment is able to predict response to treatment with the antibody-drug conjugate trastuzumab-emtansine, in patients with human epithelial growth factor-2 (HER2)-positive breast cancer. Future studies would benefit from a standardized criterion to define positive tumor uptake, possibly supported by quantitative analysis, and validated by linking imaging data with corresponding clinical outcome. Taken together, these results encourage further studies to develop (89)Zr-immuno-PET as a predictive imaging biomarker to guide individualized treatment, as well as for potential application in drug development.

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Dataset Information

Noise-Induced Variability of Immuno-PET with Zirconium-89-Labeled Antibodies: an Analysis Based on Count-Reduced Clinical Images.

Purpose

Procedures

Results

Conclusions

Publications

Noise-Induced Variability of Immuno-PET with Zirconium-89-Labeled Antibodies: an Analysis Based on Count-Reduced Clinical Images.

Similar Datasets

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