Inflammation and vascular permeability correlate with growth in sporadic vestibular schwannoma

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 (BP_ND) and DCE-MRI derived vascular biomarkers (K^trans, v_p, v_e) 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 BP_ND (−0.07 vs 0.47, P = 0.020), and higher mean tumor K^trans (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.