Correction and utilization of the washout effect in range-verification PET for particle therapy

In charged particle therapy, it is essential to verify the irradiation beam range. Thus, using positron (β+)-emitting nuclides which are produced in irradiated tissue, positron emission tomography (PET) has been studied, and clinically applied for in vivo range verification in particle therapy. However, a correction method for the biological washout effect is one of the fundamental issues for quantitative verification of the beam range; the irradiation-induced β+-emitting nuclides are affected by the pathophysiological environment such as blood perfusion. Since the biological washout effect is a tissue-specific phenomenon, extensive basic and clinical research has been conducted for modeling its kinetic process. Although considered as an undesirable factor in PET-based range validation, on the other hand, the biological washout effect may provide unique insights into the vascular status of a tumor and potentially support evaluation of the cancer pathophysiology. Consequently, this review provides a comprehensive outline of studies of the biological washout effect in particle therapy, focusing on both its correction and potential beneficial utilization.