Assessing Inflammation in Acute Intracerebral Hemorrhage with PK11195 PET and Dynamic Contrast‐Enhanced MRI

Abstract

BACKGROUND AND PURPOSE Studies in animal models suggest that inflammation is a major contributor to secondary injury after intracerebral hemorrhage (ICH). Direct, noninvasive monitoring of inflammation in the human brain after ICH will facilitate early‐phase development of anti‐inflammatory treatments. We sought to investigate the feasibility of multimodality brain imaging in subacute ICH. METHODS Acute ICH patients were recruited to undergo multiparametric MRI (including dynamic contrast‐enhanced measurement of blood‐brain barrier transfer constant (Ktrans) and PET with [11C]‐(R)‐PK11195). [11C]‐(R)‐PK11195 binds to the translocator protein 18 kDa (TSPO), which is rapidly upregulated in activated microglia. Circulating inflammatory markers were measured at the time of PET. RESULTS Five patients were recruited to this feasibility study with imaging between 5 and 16 days after onset. Etiologies included hypertension‐related small vessel disease, cerebral amyloid angiopathy (CAA), cavernoma, and arteriovenous malformation (AVM). [11C]‐(R)‐PK11195 binding was low in all hematomas and 2 (patient 2 [probable CAA] and 4 [AVM]) cases showed widespread increase in binding in the perihematomal region versus contralateral. All had increased Ktrans in the perihematomal region (mean difference = 2.2 × 10−3 minute−1; SD = 1.6 × 10−3 minute−1) versus contralateral. Two cases (patients 1 [cavernoma] and 4 [AVM]) had delayed surgery (3 and 12 months post‐onset, respectively) with biopsies showing intense microglial activation in perilesional tissue. CONCLUSIONS Our study demonstrates for the first time the feasibility of performing complex multimodality brain imaging for noninvasive monitoring of neuroinflammation for this severe stroke subtype.

Quantification of Macrophage-Driven Inflammation During Myocardial Infarction with 18F-LW223, a Novel TSPO Radiotracer with Binding Independent of the rs6971 Human Polymorphism

“…With the advent of total-body PET clinical scanners (57), assessment of multiorgan responses to disease will become increasingly important in medical research. This is attractive for TSPO-PET studies, given that TSPO has served as a marker of regional tissue inflammation in pathologies throughout the body (4,(6)(7)(8)(9)(10). In this study, we observed a significant positive correlation between the brain and heart following MI, which was detected by 18 F-LW223 PET imaging in vivo, and TSPO and CD68 staining ex-vivo.…”

“…The 18kDa translocator protein (TSPO) is expressed within the outer membrane of the mitochondria (3) where it is a key factor in controlling the transport of cholesterol necessary for steroid hormone synthesis. TSPO is highly expressed within inflammatory cells such as macrophages in the periphery (4) and microglia in the brain (5), and has consequently been used as a marker of inflammation in pathologies throughout the body (4,(6)(7)(8)(9)(10).…”

Involvement of Microglia in the Pathophysiology of Intracranial Aneurysms and Vascular Malformations—A Short Overview

“…To assess the degree of cerebral inflammation after acute hemorrhage via positron emission tomography (PET), Abid et al utilized [ 11 C]-(R)-PK11195 to highlight the perihematomal region [ 92 ]. [ 11 C]-(R)-PK11195 attaches to translocator protein 18 kDa (TSPO), whose level is promptly increased in activated microglia.…”

[125 I]IodoDPA-713 Binding to 18 kDa Translocator Protein (TSPO) in a Mouse Model of Intracerebral Hemorrhage: Implications for Neuroimaging

“…However, until very recently no such effort has been made after ICH. To this end, a study comprising of five ICH patients documented for the first time the feasibility of employing [ 11 C] labeled first generation TSPO ligand, [ 11 C]-(R)-PK11195 in monitoring microglial activation after ICH (Abid et al, 2017 ). However, given the small sample size of the aforementioned study (Abid et al, 2017 ), future work is highly warranted establishing the applicability of TSPO ligands for neuroimaging applications after ICH.…”