Hybrid¹⁸F-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

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 18 F-fluoroethyltyrosine ( 18 F-FET) perfusion PET/MRI into routine clinical practice. Methods: Through expanded-access investigational new drug use of 18 F-FET, hybrid 18 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 18 F-FET PET/MRI was dually evaluated within routine clinical service and for retrospective parametric evaluation. Various 18 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. Results: Hybrid 18 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%). 18 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, 18 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. Conclusion: Hybrid 18 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 18 F-FET PET complements MRI, even rescuing MRI when it fails.

PET Imaging of Metabolism, Perfusion, and Hypoxia

“…18 F-FET has established itself as the most commonly used amino acid radiotracer in Europe for brain tumor imaging, 74,75 with proven utility in guiding clinical management of these patients 76 . In particular, 18 F-FET has demonstrated an ability to distinguish between progression of disease and treatment-related changes, a known limitation with MRI 77 . Similarly, PET imaging with 18 F-FDOPA has demonstrated potential in brain tumor imaging, including serving as a biomarker to predict progression-free survival in glioblastoma patients with suspected tumor recurrence 78 .…”

18F-Fluoroethyl-L Tyrosine Positron Emission Tomography Radiomics in the Differentiation of Treatment-Related Changes from Disease Progression in Patients with Glioblastoma

“…In a Bayesian network meta-analysis including different PET radiotracers and MRI for recurrent glioma, 18 F-FET showed the highest sensitivity, specificity, positive predictive value, and accuracy [ 4 ]. However, when a simultaneous imaging of 18 F-FET PET and MRI obtained by a hybrid PET–MRI system comes into play, no significant differences seem to exist, probably explained by an increase in the interpretation confidence of both joined techniques [ 28 , 29 ].…”