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 with ¹⁸F-fluoromisonidazole (¹⁸F-FMISO) dynamic PET (dPET) in head and neck cancer. Methods: One hundred twenty head and neck cancer patients underwent 0- to 30-min ¹⁸F-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), and ¹⁸F-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 unbound ¹⁸F-FMISO was rapid in all tumors. ¹⁸F-FMISO distribution volume deviated from the expected value of unity, causing discrepancy between k₃ maps and total ¹⁸F-FMISO uptake and reducing the dynamic range of total ¹⁸F-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 interpreting ¹⁸F-FMISO uptake and improve the characterization of lesions. We show total acquisition times can be reduced to 20 min, facilitating the translation of ¹⁸F-FMISO dPET into the clinic.