[123I]CLINDE SPECT as a neuroinflammation imaging approach in a rat model of stroke

Abstract

Poststroke neuroinflammation exacerbates disease progression. [¹¹C]PK11195-positron emission tomography (PET) imaging has been used to visualize neuroinflammation; however, its short half-life of 20 min limits its clinical use. [¹²³I]CLINDE has a longer half-life (13h); therefore, [¹²³I]CLINDE-single-photon emission computed tomography (SPECT) imaging is potentially more practical than [¹¹C]PK11195-PET imaging in clinical settings. The objectives of this study were to 1) validate neuroinflammation imaging using [¹²³I]CLINDE and 2) investigate the mechanisms underlying stroke in association with neuroinflammation using multimodal techniques, including magnetic resonance imaging (MRI), gas-PET, and histological analysis, in a rat model of ischemic stroke, that is, permanent middle cerebral artery occlusion (pMCAo). At 6 days post-pMCAo, [¹²³I]CLINDE-SPECT considerably corresponded to the immunohistochemical images stained with the CD68 antibody (a marker for microglia/microphages), comparable to the level observed in [¹¹C]PK11195-PET images. In addition, the [¹²³I]CLINDE-SPECT images corresponded well with autoradiography images. Rats with severe infarcts, as defined by MRI, exhibited marked neuroinflammation in the peri-infarct area and less neuroinflammation in the ischemic core, accompanied by a substantial reduction in the cerebral metabolic rate of oxygen (CMRO₂) in ¹⁵O-gas-PET. Rats with moderate-to-mild infarcts exhibited neuroinflammation in the ischemic core, where CMRO₂ levels were mildly reduced. This study demonstrates that [¹²³I]CLINDE-SPECT imaging is suitable for neuroinflammation imaging and that the distribution of neuroinflammation varies depending on the severity of infarction.

Keywords: CMRO(2); Ischemic stroke; Multimodal imaging; Neuroinflammation; PET; Permanent MCAo; SPECT; TSPO ligand; [(11)C]PK11195; [(123)I]CLINDE.