TH-D-304A-06: Comparison of Cu-ATSM and FMISO Uptake to Variations in Oxygen Tension

Abstract

Purpose: Unique uptake and retention mechanisms of PET hypoxia tracers make comparison between them challenging. Two common hypoxia surrogates, [ 61 Cu ]Cu‐ATSM and [ 18 F ]FMISO, were compared by modeling their uptake as a function of local oxygen tension and comparing these with clinical measurements. Materials and Methods: An electrochemical formalism describing bioreductive retention mechanisms under equilibrium conditions was adopted to relate time‐averaged tracer concentration to tissue partial oxygen tension (pO2). Chemical equilibrium constants describing product concentration to reactant concentration ratios were determined from free energy changes and reduction‐oxidation potentials of the most probable reactions. Calculated pO2 distributions from imaged Cu‐ATSM tracer activity concentrations of head and neck squamous cell carcinoma (HNSCC) patients were compared to microelectrode pO2 measurements in 69 patients with HNSCC. Additionally, simulated Cu‐ATSM and FMISO uptake distributions were derived from the mean HNSCC population pO2 distribution. Results: Cu‐ATSM and FMISO uptake differ in sensitivity to changes in oxygen tension, as Cu‐ATSM finely samples low pO2 over broad uptake ranges while FMISO uniformly samples pO2 above low pO2 distribution peaks. Cu‐ATSM uptake is higher than FMISO uptake under severe hypoxia (pO2 10 mmHg) FMISO is retained more than Cu‐ATSM. Based on population averages, clinical hypoxia thresholds (5 mmHg and 2.5 mmHg) correspond to higher Cu‐ATSM SUV (3.1 and 3.7) and lower FMISO SUV (1.2 and 2.4). Conclusions: Differing retention mechanisms of Cu‐ATSM and FMISO make direct comparison inaccurate without relating their uptake to common metrics. Results indicate that Cu‐ATSM is more selective for low pO2 than FMISO and may explain the relatively low correlation between uptakes of these tracers in certain small animal models. When using various hypoxia tracers as a basis for dose painting, uptake and resulting dose distributions should not be interpreted interchangeably but rather as yielding complementary information.