Feasibility of Mapping Transient Tumor Hypoxia Using in Situ Activation PET Imaging: A Simulation Study
E Dalah1*, c yang2, I Moraru3, E Paulson4, Q Zhang5, Y Hu6, X Li7, (1) Medical College of Wisconsin, Milwaukee, WI, (2) ,,,(3) Medical College of Wisconsin, Milwaukee, WI, (4) Medical College of Wisconsin, Milwaukee, WI, (5) 2Wu Xi Yi Ren Tumor Hosiptal, Wu Xi, Jiang Su, (6) Cancer Institute, CAMS, Beijing, ,(7) Medical College of Wisconsin, Milwaukee, WITH-E-BRA-4 Thursday 1:00:00 PM - 2:50:00 PM Room: Ballroom A
Purpose: Detecting transient tumor hypoxia in real-time is desirable and has been challenging in radiation therapy. Here, we explore the feasibility of mapping tumor transient hypoxia in real-time using in situ activation by high-energy photons.
Methods: The simulation used spatial uptake of a hypoxia tracer (e.g. 64Cu-ATSM) in PET or autoradiograph as a surrogate for micro-vessel density, which was then used to generate a steady state oxygen tension (pO2) map using a reaction diffusion model. The 15O in situ activation map by high-energy photons was generated using Ten Haken model based on the steady state pO2 map with the addition of element composition. The activation map includes both mobile and immobile 15O. The mobile 15O component was isolated by subtracting the fast decay portion from the overall decay curve. The simulation process was coded in Matlab using photon energies of 20 - 50MeV.
Results: The diffusion model shows heterogeneous distribution of pO2 ranges from 28 - 1.9 mmHg for a pancreas tumor model, depending on simulation baseline values, tumor vasculature structure and architecture. The threshold of 63% of the mean image intensity on the in situ activation PET image was found to reasonably agree with original hypoxia map using 5 mmHg as a cutoff value. The simulated transient hypoxic fraction was comparable with measurements reported using 64Cu-ATSM autoradiography, e.g., measurement of 0.166 ± 0.067 versus simulation of 0.157.
Conclusions: It is feasible to detect transient tumor hypoxia with oxygen in situ activation using high-energy photons. This opens door for tracking tumor transient hypoxia in real-time during the delivery of radiation therapy. Immediate future work includes quantifying the in situ activation PET (e.g., 15O activity in terms of pO2 in mmHg), and in-vivo measurement of the in situ activation.