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Quantification of Tumor Hypoxic Fractions Using Positron Emission Tomography with [18F]Fluoromisonidazole ([18F]FMISO) Kinetic Analysis and Invasive Oxygen Measurements

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Abstract

Purpose

The purpose of this study is to use dynamic [18F]fluoromisonidazole ([18F]FMISO) positron emission tomography (PET) to compare estimates of tumor hypoxic fractions (HFs) derived by tracer kinetic modeling, tissue-to-blood ratios (TBR), and independent oxygen (pO2) measurements.

Procedures

BALB/c mice with EMT6 subcutaneous tumors were selected for PET imaging and invasive pO2 measurements. Data from 120-min dynamic [18F]FMISO scans were fit to two-compartment irreversible three rate constant (K 1, k 2, k 3) and Patlak models (K i). Tumor HFs were calculated and compared using K i, k 3, TBR, and pO2 values. The clinical impact of each method was evaluated on [18F]FMISO scans for three non-small cell lung cancer (NSCLC) radiotherapy patients.

Results

HFs defined by TBR (≥1.2, ≥1.3, and ≥1.4) ranged from 2 to 85 % of absolute tumor volume. HFs defined by K i (>0.004 ml min cm−3) and k 3 (>0.008 min−1) varied from 9 to 85 %. HF quantification was highly dependent on metric (TBR, k 3, or K i) and threshold. HFs quantified on human [18F]FMISO scans varied from 38 to 67, 0 to 14, and 0.1 to 27 %, for each patient, respectively, using TBR, k 3, and K i metrics.

Conclusions

[18F]FMISO PET imaging metric choice and threshold impacts hypoxia quantification reliability. Our results suggest that tracer kinetic modeling has the potential to improve hypoxia quantification clinically as it may provide a stronger correlation with direct pO2 measurements.

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Acknowledgments

This work was partially supported by a Yale Cancer Center Pilot grant, Yale PET center Pilot funds, and a Helmholtz International Graduate School PhD Fellowship. The authors have nothing to disclose.

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Authors and Affiliations

  1. Department of Therapeutic Radiology, Yale University School of Medicine, P.O. Box 208040, New Haven, CT, 06520-8040, USA

    Olivia J. Kelada, Sara Rockwell, Yanfeng Liu, Roy H. Decker & David J. Carlson

  2. Department of Medical Physics in Radiation Oncology, German Cancer Research Center, Heidelberg, Germany

    Olivia J. Kelada & Uwe Oelfke

  3. Department of Pharmacology, Yale University School of Medicine, New Haven, CT, USA

    Sara Rockwell

  4. Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, CT, USA

    Ming-Qiang Zheng, Yiyun Huang & Richard E. Carson

  5. Section of Comparative Medicine, Yale University School of Medicine, New Haven, CT, USA

    Carmen J. Booth

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  1. Olivia J. Kelada
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Correspondence to David J. Carlson.

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Kelada, O.J., Rockwell, S., Zheng, MQ. et al. Quantification of Tumor Hypoxic Fractions Using Positron Emission Tomography with [18F]Fluoromisonidazole ([18F]FMISO) Kinetic Analysis and Invasive Oxygen Measurements. Mol Imaging Biol 19, 893–902 (2017). https://doi.org/10.1007/s11307-017-1083-9

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