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

PURPOSE

The purpose of this study is to use dynamic [F]fluoromisonidazole ([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 (pO) measurements.

PROCEDURES

BALB/c mice with EMT6 subcutaneous tumors were selected for PET imaging and invasive pO measurements. Data from 120-min dynamic [F]FMISO scans were fit to two-compartment irreversible three rate constant (K , k , k ) and Patlak models (K ). Tumor HFs were calculated and compared using K , k , TBR, and pO values. The clinical impact of each method was evaluated on [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 (>0.004 ml min cm) and k (>0.008 min) varied from 9 to 85 %. HF quantification was highly dependent on metric (TBR, k , or K ) and threshold. HFs quantified on human [F]FMISO scans varied from 38 to 67, 0 to 14, and 0.1 to 27 %, for each patient, respectively, using TBR, k , and K metrics.

CONCLUSIONS

[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 pO measurements.