Inflammation and vascular permeability correlate with growth in sporadic vestibular schwannoma.
Adult
Aged
Aged, 80 and over
Calcium-Binding Proteins
/ metabolism
Capillary Permeability
Carbon Radioisotopes
Case-Control Studies
Disease Progression
Female
Fibrinogen
/ metabolism
Humans
Immunohistochemistry
Inflammation
Isoquinolines
Ki-67 Antigen
/ metabolism
Magnetic Resonance Imaging
Male
Microfilament Proteins
/ metabolism
Middle Aged
Neuroma, Acoustic
/ diagnostic imaging
Platelet Endothelial Cell Adhesion Molecule-1
/ metabolism
Positron-Emission Tomography
Receptors, GABA
/ metabolism
S100 Proteins
/ metabolism
Tumor Burden
DCE-MRI
PET imaging
TSPO
inflammation
vestibular schwannoma
Journal
Neuro-oncology
ISSN: 1523-5866
Titre abrégé: Neuro Oncol
Pays: England
ID NLM: 100887420
Informations de publication
Date de publication:
19 02 2019
19 02 2019
Historique:
pubmed:
6
11
2018
medline:
6
5
2020
entrez:
3
11
2018
Statut:
ppublish
Résumé
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 tracer 11C-(R)-PK11195 and dynamic contrast enhanced (DCE) MRI derived vascular biomarkers. Nineteen patients with sporadic VS (8 static, 7 growing, and 4 shrinking tumors) underwent prospective imaging with dynamic 11C-(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. 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. 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.
Sections du résumé
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 tracer 11C-(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 dynamic 11C-(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.
Identifiants
pubmed: 30388263
pii: 5155625
doi: 10.1093/neuonc/noy177
pmc: PMC6380424
doi:
Substances chimiques
AIF1 protein, human
0
Calcium-Binding Proteins
0
Carbon Radioisotopes
0
Carbon-11
0
Isoquinolines
0
Ki-67 Antigen
0
MKI67 protein, human
0
Microfilament Proteins
0
PECAM1 protein, human
0
Platelet Endothelial Cell Adhesion Molecule-1
0
Receptors, GABA
0
S100 Proteins
0
TSPO protein, human
0
Fibrinogen
9001-32-5
PK 11195
YNF83VN1RL
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
314-325Informations de copyright
© The Author(s) 2018. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.
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