Washout in in-beam PET as a biomarker of tumor vascular condition: a feasibility study in rats

Positron emission tomography (PET) has been used for treatment verification in charged particle therapy. For accurate dose verification, modeling and correction of the biological washout effect of the positron emitters, which is influenced by the tumor vasculature condition, has been an issue. Conversely, the biological washout effect indicates changes of the tumor vasculature condition, which is known to influence radiation response. At present, blood circulatory changes in a tumor are measured using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to evaluate tumor radiation response. Here, measuring the biological washout rate of the produced positron emitters may also function to evaluate tumor radiation response, in a similar manner to DCE-MRI. Therefore, this study compared the washout rates between in-beam PET during ¹² C ion beam irradiation and DCE-MRI. Different vascular types of the tumor model were prepared using six nude rats. The tumor of each nude rat was irradiated by a ¹² C ion beam and scanned by in-beam PET on the first day. On the second day, the DCE-MRI experiment was performed for the same six nude rats. The washout rate of the produced positron emitters (k 2,1st ) and the MRI contrast agent (k 2a ) were derived using the single tissue compartment model. A linear correlation was observed between k 2,1st and k 2a , and they were inversely related to fractional necrotic volume. This is the first study which showed the feasibility of washout in in-beam PET as a biomarker for the tumor vascular condition; a clear correlation was seen between the washout rate of the positron emitters in tumor tissue produced via a nuclear fragmentation reaction and the washout of the MRI contrast agent administrated intravenously.