Multiparametric Imaging of Tumor Hypoxia and Perfusion with18F-Fluoromisonidazole Dynamic PET in Head and Neck Cancer.
Tumor hypoxia and perfusion are independent prognostic indicators of patient outcome. We developed the methodology for and investigated the utility of multiparametric imaging of tumor hypoxia and perfusion with18F-fluoromisonidazole (18F-FMISO) dynamic PET (dPET) in head and neck cancer.Methods:One hundred twenty head and neck cancer patients underwent 0- to 30-min18F-FMISO dPET in a customized immobilization mask, followed by 10-min static acquisitions starting at 93 ± 6 and 160 ± 13 min after injection. A total of 248 lesions (≥2 cm3) were analyzed. Voxelwise pharmacokinetic modeling was conducted using an irreversible 1-plasma 2-tissue-compartment model to calculate surrogate biomarkers of tumor hypoxia (k3), perfusion (K1), and18F-FMISO distribution volume. The analysis was repeated with truncated dPET datasets.Results:Substantial inter- and intratumor heterogeneity was observed for all investigated metrics. Equilibration between the blood and unbound18F-FMISO was rapid in all tumors.18F-FMISO distribution volume deviated from the expected value of unity, causing discrepancy betweenk3maps and total18F-FMISO uptake and reducing the dynamic range of total18F-FMISO uptake for quantifying the degree of hypoxia. Both positive and negative trends between hypoxia and perfusion were observed in individual lesions. All investigated metrics were reproducible when calculated from a truncated 20-min dataset.Conclusion:18F-FMISO dPET provides the data necessary to generate parametric maps of tumor hypoxia, perfusion, and radiotracer distribution volume. These data clarify the ambiguity in interpreting18F-FMISO uptake and improve the characterization of lesions. We show total acquisition times can be reduced to 20 min, facilitating the translation of18F-FMISO dPET into the clinic.
Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York grkovskm@mkscc.org.
Milan
M
Grkovski
Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York; and.
Heiko
H
Schöder
Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.
Nancy Y
NY
Lee
Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York; and.
Sean D
SD
Carlin
Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York.
Bradley J
BJ
Beattie
Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.
Nadeem
N
Riaz
Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.
Jonathan E
JE
Leeman
Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York.
Joseph A
JA
O'Donoghue
Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York.
John L
JL
Humm
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006258:Head and Neck Neoplasms / Q000098:blood supply / Q000175:diagnosis* / Q000378:metabolism*; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods; D008297:Male; D008875:Middle Aged; D008920:Misonidazole / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D064847:Multimodal Imaging / Q000379:methods; D009389:Neovascularization, Pathologic / Q000097:blood / Q000175:diagnosis* / Q000378:metabolism*; D015588:Observer Variation; D010100:Oxygen / Q000378:metabolism; D055420:Perfusion Imaging / Q000379:methods; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D000072258:Tumor Hypoxia
D019275:Radiopharmaceuticals; C031843:fluoromisonidazole; D008920:Misonidazole; D010100:Oxygen
18F-fluoromisonidazole; FMISO; dynamic PET; head and neck cancer; hypoxia; perfusion