Hybrid<sup>18</sup>F-Fluoroethyltyrosine PET and MRI with Perfusion to Distinguish Disease Progression from Treatment-Related Change in Malignant Brain Tumors: The Quest to Beat the Toughest Cases
Nathaniel J. Smith, Tristan K. Deaton, Wendy Territo, Brian Graner, Andrew J. Gauger, Scott E. Snyder, M. Schulte, Mark A. Green, Gary D. Hutchins, Michael C. Veronesi
Abstract
Conventional MRI has important limitations when assessing for progression of disease (POD) versus treatment-related changes (TRC) in patients with malignant brain tumors. We describe the observed impact and pitfalls of implementing <sup>18</sup>F-fluoroethyltyrosine (<sup>18</sup>F-FET) perfusion PET/MRI into routine clinical practice. <b>Methods:</b> Through expanded-access investigational new drug use of <sup>18</sup>F-FET, hybrid <sup>18</sup>F-FET perfusion PET/MRI was performed during clinical management of 80 patients with World Health Organization central nervous system grade 3 or 4 gliomas or brain metastases of 6 tissue origins for which the prior brain MRI results were ambiguous. The diagnostic performance with <sup>18</sup>F-FET PET/MRI was dually evaluated within routine clinical service and for retrospective parametric evaluation. Various <sup>18</sup>F-FET perfusion PET/MRI parameters were assessed, and patients were monitored for at least 6 mo to confirm the diagnosis using pathology, imaging, and clinical progress. <b>Results:</b> Hybrid <sup>18</sup>F-FET perfusion PET/MRI had high overall accuracy (86%), sensitivity (86%), and specificity (87%) for difficult diagnostic cases for which conventional MRI accuracy was poor (66%). <sup>18</sup>F-FET tumor-to-brain ratio static metrics were highly reliable for distinguishing POD from TRC (area under the curve, 0.90). Dynamic tumor-to-brain intercept was more accurate (85%) than SUV slope (73%) or time to peak (73%). Concordant PET/MRI findings were 89% accurate. When PET and MRI conflicted, <sup>18</sup>F-FET PET was correct in 12 of 15 cases (80%), whereas MRI was correct in 3 of 15 cases (20%). Clinical management changed after 88% (36/41) of POD diagnoses, whereas management was maintained after 87% (34/39) of TRC diagnoses. <b>Conclusion:</b> Hybrid <sup>18</sup>F-FET PET/MRI positively impacted the routine clinical care of challenging malignant brain tumor cases at a U.S. institution. The results add to a growing body of literature that <sup>18</sup>F-FET PET complements MRI, even rescuing MRI when it fails.