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

Abstract

Intracerebral hemorrhage (ICH) is a fatal stroke subtype with significant public health impact. Although neuroinflammation is a leading cause of neurological deficits after ICH, no imaging tool is currently available to monitor brain inflammation in ICH patients. Given the role of TSPO in neuroinflammation, herein we investigate whether a second-generation TSPO ligand, [125 I]IodoDPA-713 can be used to monitor the changes in TSPO expression in a preclinical model of intracerebral hemorrhage. Male CD1 mice were subjected to ICH/Sham. The brain sections, collected at different time points were incubated with [125 I]IodoDPA-713 and the brain uptake of [125 I]IodoDPA-713 was estimated using autoradiography. The specificity of [125 I]IodoDPA-713 binding was confirmed by a competitive displacement study with an unlabeled TSPO ligand, PK11195. [125 I]IodoDPA-713 binding was higher in the ipsilateral striatum with an enhanced binding observed in the peri-hematomal brain region after ICH, whereas the brain sections from sham as well as contralateral brain areas of ICH exhibited marginal binding of [125 I]IodoDPA-713. PK11195 completely reversed the [125 I] IodoDPA-713 binding to brain sections suggesting a specific TSPO-dependent binding of [125 I]IodoDPA-713 after ICH. This was further confirmed with immunohistochemistry analysis of adjacent sections, which revealed a remarkable expression of TSPO in the areas of high [125 I]IodoDPA-713 binding after ICH. The specific as well as enhanced binding of [125 I]IodoDPA-713 to the ipsilateral brain areas after ICH as assessed by autoradiography analysis provides a strong rationale for testing the applicability of [125 I]IodoDPA-713 for non-invasive neuroimaging in preclinical models of ICH.

Usefulness of postoperative serum translocator protein as a predictive marker for delirium after breast cancer surgery in elderly women

“…However, there is significant evidence that TP can be an inflammatory biomarker that reflects the inflammatory status of various acute brain injury diseases, such as acute intracerebral hemorrhage, ischemic stroke, acute traumatic brain injury, and spontaneous subarachnoid hemorrhage. 28–31 This study showed that postoperative serum TP levels were significantly elevated compared with preoperative serum TP levels in breast cancer patients and fasting serum TP levels in healthy and benign controls. Intriguingly, serum C-reactive protein levels were also independently correlated with postoperative serum TP levels after correcting for other possible confounding factors, such as tumor size and histological type.…”

“…26,27 Elevated TP levels in peripheral blood have been reported to be highly associated with the severity and outcome of patients with acute ischemic stroke, acute intracerebral hemorrhage, spontaneous subarachnoid hemorrhage, and severe traumatic brain injury. [28][29][30][31] Thus, TP is considered an inflammatory biomarker that reflects the level of brain injury. However, it is unclear if there is a relationship between circulating TP levels and POD.…”

MicroPET Imaging Assessment of Brain Tau and Amyloid Deposition in 6 × Tg Alzheimer’s Disease Model Mice

“…The abundance of translocator protein (TSPO), located predominantly in glial cells, is low in normal brain tissue but markedly increased in pathological conditions associated with microglial or astrocytic activation [ 8 ]. Therefore, TSPO is considered an ideal target for neuroinflammation imaging using PET [ 9 , 10 , 11 , 12 ]. [ 18 F]DPA714 is a promising radiotracer targeting TSPO to investigate neuroinflammation [ 12 ].…”