The 18-kDa mitochondrial translocator protein in human gliomas: an 11C-(R)PK11195 PET imaging and neuropathology study.
The 18-kDa mitochondrial translocator protein (TSPO) is upregulated in high-grade astrocytomas and can be imaged by PET using the selective radiotracer (11)C-(R)PK11195. We investigated (11)C-(R)PK11195 binding in human gliomas and its relationship with TSPO expression in tumor tissue and glioma-associated microglia/macrophages (GAMs) within the tumors.


METHODS
Twenty-two glioma patients underwent dynamic (11)C-(R)PK11195 PET scans and perfusion MR imaging acquisition. Parametric maps of (11)C-(R)PK11195 binding potential (BPND) were generated. Coregistered MR/PET images were used to guide tumor biopsy. The tumor tissue was quantitatively assessed for TSPO expression and infiltration of GAMs using immunohistochemistry and double immunofluorescence. The imaging and histopathologic parameters were compared among different histotypes and grades and correlated with each other.


RESULTS
BPND of (11)C-(R)PK11195 in high-grade gliomas was significantly higher than in low-grade astrocytomas and low-grade oligodendrogliomas. TSPO in gliomas was expressed predominantly by neoplastic cells, and its expression correlated positively with BPND in the tumors. GAMs only partially contributed to the overall TSPO expression within the tumors, and TSPO expression in GAMs did not correlate with tumor BPND.


CONCLUSIONS
PET with (11)C-(R)PK11195 in human gliomas predominantly reflects TSPO expression in tumor cells. It therefore has the potential to effectively stratify patients who are suitable for TSPO-targeted treatment.
Wolfson Molecular Imaging Center, University of Manchester, Manchester, United Kingdom.
Zhangjie
Z
Su
Division of Brain Science, Imperial College London, London, United Kingdom.
Federico
F
Roncaroli
Division of Brain Science, Imperial College London, London, United Kingdom.
Pascal F
PF
Durrenberger
Wolfson Molecular Imaging Center, University of Manchester, Manchester, United Kingdom Department of Neurosurgery, Salford Royal NHS Foundation Trust, Salford, United Kingdom.
David J
DJ
Coope
Department of Neurosurgery, Salford Royal NHS Foundation Trust, Salford, United Kingdom.
Konstantina
K
Karabatsou
Wolfson Molecular Imaging Center, University of Manchester, Manchester, United Kingdom.
Rainer
R
Hinz
Wolfson Molecular Imaging Center, University of Manchester, Manchester, United Kingdom.
Gerard
G
Thompson
Center for Neuroimaging, Institute of Psychiatry, King's College London, London, United Kingdom.
Federico E
FE
Turkheimer
Division of Brain Science, Imperial College London, London, United Kingdom.
Karolina
K
Janczar
Neuropathology Unit, Salford Royal NHS Foundation Trust, Salford, United Kingdom; and.
Daniel
D
Du Plessis
Department of Neurosurgery, The Walton Center NHS Foundation Trust, Liverpool, United Kingdom.
Andrew
A
Brodbelt
Wolfson Molecular Imaging Center, University of Manchester, Manchester, United Kingdom.
Alan
A
Jackson
Wolfson Molecular Imaging Center, University of Manchester, Manchester, United Kingdom.
Alexander
A
Gerhard
Wolfson Molecular Imaging Center, University of Manchester, Manchester, United Kingdom karl.herholz@manchester.ac.uk.
Karl
K
Herholz
D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001254:Astrocytoma / Q000000981:diagnostic imaging; D014408:Biomarkers, Tumor; D001812:Blood-Brain Barrier; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology; D001932:Brain Neoplasms / Q000000981:diagnostic imaging*; D002250:Carbon Radioisotopes; D002471:Cell Transformation, Neoplastic; D005260:Female; D005910:Glioma / Q000000981:diagnostic imaging*; D006801:Humans; D061705:Image-Guided Biopsy; D007546:Isoquinolines / Q000627:therapeutic use*; D008024:Ligands; D008264:Macrophages / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D017628:Microglia / Q000378:metabolism; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods*; D055815:Young Adult
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D002250:Carbon Radioisotopes; D007546:Isoquinolines; D008024:Ligands; C037850:PK 11195
11C-(R)PK11195; PET; glioma; microglia; translocator protein