| Summary: | <sup>18</sup>F-FDG Positron Emission Tomography (PET) is used to monitor tumor response to <sup>131</sup>I-therapy, but is confounded by prompt emissions (284, 364, 637, and 723 keV) from <sup>131</sup>I, particularly in animal PET imaging. We propose a method for correcting this emission in <sup>18</sup>F-FDG PET. The <sup>131</sup>I prompt emission effect was assessed within various energy windows and various activities. We applied a single gamma correction method to a phantom and in vivo mouse model. The <sup>131</sup>I prompt emission fraction was 12% when 300 µCi of <sup>131</sup>I and 100 µCi of FDG were administered, and increased exponentially with escalating <sup>131</sup>I activity for all energy windows. The difference in spill-over ratio was reduced to <5% after <sup>131</sup>I prompt emission correction. In the mouse model, the standard uptake value (SUV) did not differ significantly between FDG PET only (gold standard) and FDG PET after <sup>131</sup>I prompt emission-correction, whereas it was overestimated by 38% before correction. Contrast was improved by 18% after <sup>131</sup>I prompt emission correction. We first found that count contamination on <sup>18</sup>F-FDG follow-up scans due to <sup>131</sup>I spilled-over count after <sup>131</sup>I rituximab tumor targeted therapy. Our developed <sup>131</sup>I prompt emission-correction method increased accuracy during measurement of standard uptake values on <sup>18</sup>F-FDG PET.
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