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

Purpose The purpose of this study is to use dynamic [ 18 F]fluoromisonidazole ([ 18 F]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 ( p O 2 ) measurements. Procedures BALB/c mice with EMT6 subcutaneous tumors were selected for PET imaging and invasive p O 2 measurements. Data from 120-min dynamic [ 18 F]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 p O 2 values. The clinical impact of each method was evaluated on [ 18 F]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 [ 18 F]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 [ 18 F]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 p O 2 measurements.