A mathematical approach towards simulating a realistic tissue activity curve of 64Cu-ATSM for the purpose of sub-target volume delineation in radiotherapy

One unique feature of positron emission tomography (PET) is that it allows measurements of regional tracer concentration in hypoxic tumour-bearing tissue, supporting the need for accurate radiotherapy treatment planning. Generally the data are taken over multiple time frames, in the form of tissue activity curves (TACs), providing an indication of the presence of hypoxia, the degree of oxygen perfusion, vascular geometry and hypoxia fraction. In order to understand such a complicated phenomenon a number of theoretical studies have attempted to describe tracer uptake in tissue cells. More recently, a novel computerized reaction diffusion equation method developed by Kelly and Brady has allowed simulation of the realistic TACs of 18F-FMISO, with representation of physiological oxygen heterogeneity and tracer kinetics. We present a refinement to the work of Kelly and Brady, with a particular interest in simulating TACs of the most promising hypoxia selective tracer, 64Cu-ATSM, demonstrating its potential role in tumour sub-volume delineation for radiotherapy treatment planning. Simulation results have demonstrated the high contrast of imaging using ATSM, with a tumour to blood ratio ranging 2.24–4.1. Similarly, results of tumour sub-volumes generated using three different thresholding methods were all well correlated.