SPECT imaging of glioma with radioiodinated CLINDE: evidence from a mouse GL26 glioma model

Abstract

BackgroundRecent research has demonstrated the potential of 18-kDa translocator protein (TSPO) to serve as a target for nuclear imaging of gliomas. The aim of this study was to evaluate SPECT imaging of GL26 mouse glioma using radioiodinated CLINDE, a TSPO-specific tracer.MethodsGL26 cells, previously transfected with an enhanced green fluorescent protein (EGFP)-expressing lentivirus, were stereotactically implanted in the striatum of C57/Bl6 mice. At 4 weeks post-injection, dynamic SPECT scans with [123I]CLINDE were performed. A displacement study assessed specificity of tracer binding. SPECT images were compared to results of autoradiography, fluorescence microscopy, in situ nucleic acid hybridization, histology, and immunohistochemistry. Western blotting was performed to verify TSPO production by the tumor.ResultsSpecific uptake of tracer by the tumor is observed with a high signal-to-noise ratio. Tracer uptake by the tumor is indeed 3.26 ± 0.32 times higher than that of the contralateral striatum, and 78% of the activity is displaceable by unlabeled CLINDE. Finally, TSPO is abundantly expressed by the GL26 cells.ConclusionsThe present study demonstrates the feasibility of [123I]CLINDE SPECT in translational studies and underlines its potential for clinical glioma SPECT imaging.

TSPO and amyloid deposits in sub-regions of the hippocampus in the 3xTgAD mouse model of Alzheimer’s disease

“…Secondly, as the increase in TSPO in 3xTgAD brains appears to be a subtle and localized phenomenon, its detection by SPECT could be compromised by the detection limit of the SPECT camera and the partial volume effects. This idea is in accordance with previous AD studies (Janssen et al, 2016) and with others reporting high and quantifiable TSPO levels induced by exogenous manipulations (Mattner et al, 2011;Sridharan et al, 2017;Tsartsalis et al, 2015). Furthermore, as demonstrated by our in vivo displacement study, the TSPO signal in the cerebellum is, at least in part, specific.…”

“…The aim of the present study was to investigate the efficacy of a TSPO radiotracer and to determine the time-course of the appearance of TSPO and amyloid deposits in a mouse model of AD combining amyloidosis and tauopathy. We used CLINDE, as this radiotracer has recently been shown to be effective in detecting the presence of TSPO-positive glioma cells in mice brain (Tsartsalis et al, 2015).…”

“…To determine the specificity of the  125 I-CLINDE signal, we used SPECT examinations from a previous study whose aim was to detect TSPO in response to GL26 cell injections in the striatum (Tsartsalis et al, 2015). Eighty-two minutes after the injection of the radiotracer, 4 animals received 10 mg/kg of non-radioactive CLINDE.…”

TSPO Imaging in Glioblastoma Multiforme: A Direct Comparison Between 123I-CLINDE SPECT, 18F-FET PET, and Gadolinium-Enhanced MR Imaging

“…In tissue resected from patients with astrocytoma, TSPO density correlates positively with malignancy and cell proliferation index and negatively with survival (9). 6-chloro-2-(49-123 I-iodophenyl)-3-(N,N-diethyl)-imidazo[1,2-a]pyridine-3-acetamide SPECT ( 123 I-CLINDE; MAP Medical Technologies) has been validated as a second-generation TSPO tracer for use in humans (10) and recently in a GL26 mouse model of glioma (11). We present 123 I-CLINDE SPECT, 18 F-FET PET, and gadolinium-enhanced MR imaging results from 3 GBM patients at baseline compared with contrast-enhanced structural imaging at follow-up and hypothesize that 123 I-CLINDE SPECT at baseline is an imaging biomarker of GBM progression.…”

In vivo absolute quantification of striatal and extrastriatal D2/3 receptors with [123I]epidepride SPECT

“…To estimate the plasma input function in in vivo SPECT experiments, only whole-blood radioactivity was measured individually and the free, non-metabolized radiotracer fraction was fitted using a model estimated in an independent experiment. Indeed, metabolite correction and plasma protein binding analysis for the estimation of radiotracer plasma input function was performed in an independent group of 4 rats, as previously described [27,28,[43][44][45][46] (the radioactive doses employed in this experiment are presented in Table 1). The analysis was performed in MATLAB software R2019 (Mathworks, USA).…”