Angiogenesis PET/MRI predicts initial growth of sporadic vestibular schwannomas: a prospective study with follow-up in 29 patients using [

backgroundVestibular schwannomas (VS) are benign tumors located at the cerebellopontine angle. Although benign, the growth of VS can result in significant morbidity and potential compression of adjacent structures if left untreated. An MRI of the cerebellopontine angle is the standard-of-care examination when diagnosing a VS. 75% of newly diagnosed VS undergo conservative management with follow-up scans every 6-12th months. No robust clinical prognostic marker of initial sVS tumor growth exists. We performed a phase 2 clinical trial evaluating whether our PET tracer [68Ga]Ga-NODAGA-E[c(RGDyK)]2 could be used to predict initial sVS growth rate. The study was a non-randomized prospective clinical phase II study. 43 patients were included, either with a newly MRI-verified sporadic VS (sVS) or in a watchful waiting regime, with only one follow-up MRI scan. All patients were injected intravenously with approximately 200 MBq of the tracer followed by a sequential whole-body dynamic PET/MR scan of 60 min. All volume measurements were performed on T1 w sequences after intravenous gadolinium contrast injection in the Mirada DBx software version 1.2.0. A volume of interest (VOI) was drawn to encompass the lesion on PET images and a maximal standardized uptake value (SUVmax) for the sVS was registered. Growth over time was expressed as initial relative growth rate.

resultsOf the 37 patients initially scanned, results for the first 6 months of follow-up MRI scans are available for 29 of the included patients. The tracer demonstrated stable tumor retention and a high tumor-to-background uptake. SUVmax correlates to the initial growth rate of sVS with a correlation of 0.477 (CI = 0.13–0.72, P = 0.009). A receiver operating characteristic was performed with an area under the curve of 0.7. For the detection of growing tumors (> 20% relative growth annually), a cut-off at 0.555 could be established with a sensitivity of 100% and a specificity of 73% for detecting growing tumors.

conclusionsThis study presents the largest PET-MRI study performed in patients with sporadic vestibular schwannomas. Using the PET tracer [68Ga]Ga-NODAGA-E[c(RGDyK)]2, targeting αvβ3 integrins, we found a significant correlation between uptake of the PET tracer at an initial scan and the initial relative growth rate as measured volumetric on consecutive MRI scans.

trial registrationNCT, NCT03393689. Registered 02 january 2018, https//clinicaltrials.gov/study/NCT03393689.