Inflammation and vascular permeability correlate with growth in sporadic vestibular schwannoma

Daniel Lewis, Federico Roncaroli, Erjon Agushi, Dominic Mosses, Ricky Williams, Ka-Loh Li, Xiaoping Zhu, Rainer Hinz, Ross Atkinson, Andrea Wadeson, Sharon Hulme, Helen Mayers, Emma Stapleton, Simon K L Lloyd, Simon R Freeman, Scott A Rutherford, Charlotte Hammerbeck-Ward, D Gareth Evans, Omar Pathmanaban, Alan JacksonAndrew T King, David J Coope

Research output: Contribution to journalArticlepeer-review


Background: Inflammation is hypothesized to be a key event in the growth of sporadic vestibular schwannoma (VS). In this study we sought to investigate the relationship between inflammation and tumor growth in vivo using the PET tracer11C-(R)-PK11195 and dynamic contrast enhanced (DCE) MRI derived vascular biomarkers.

Methods: Nineteen patients with sporadic VS (8 static, 7 growing, and 4 shrinking tumors) underwent prospective imaging with dynamic11C-(R)-PK11195 PET and a comprehensive MR protocol, including high temporal resolution DCE-MRI in 15 patients. An intertumor comparison of 11C-(R)-PK11195 binding potential (BPND) and DCE-MRI derived vascular biomarkers (Ktrans, vp, ve) across the 3 different tumor growth cohorts was undertaken. Tissue of 8 tumors was examined with immunohistochemistry markers for inflammation (Iba1), neoplastic cells (S-100 protein), vessels (CD31), the PK11195 target translocator protein (TSPO), fibrinogen for vascular permeability, and proliferation (Ki-67). Results were correlated with PET and DCE-MRI data.

Results: Compared with static tumors, growing VS displayed significantly higher mean 11C-(R)-PK11195 BPND (−0.07 vs 0.47, P = 0.020), and higher mean tumor Ktrans (0.06 vs 0.14, P = 0.004). Immunohistochemistry confirmed the imaging findings and demonstrated that TSPO is predominantly expressed in macrophages. Within growing VS, macrophages rather than tumor cells accounted for the majority of proliferating cells.

Conclusion: We present the first in vivo imaging evidence of increased inflammation within growing sporadic VS. Our results demonstrate that 11C-(R)-PK11195 specific binding and DCE-MRI derived parameters can be used as imaging biomarkers of inflammation and vascular permeability in this tumor group.
Original languageEnglish
Pages (from-to)314-325
Number of pages12
Issue number3
Early online date2 Nov 2018
Publication statusPublished - Mar 2019


  • vestibular schwannoma
  • inflammation
  • TSPO
  • PET imaging


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