Table 6.

Overview of the preclinical TSPO-PET/SPECT imaging studies in Huntington’s disease models

PET/SPECT tracer	Rational	HD model and species	Imaging time points	Main imaging findings	Additional readouts	Ref.
[125I]CLINDE	Characterization and validation of the tracer at different stages of excitotoxic lesion	QA (*); 75, 150, 300 nmol in male Wistar rats	6 days post-injection	• Specificity confirmed with PK1195 blocking studies (-82% decrease). • Significant [125I]CLINDE uptake increase in lesioned compared to intact side	Autoradiographic analysis (including blocking) and IHC confirmed in vivo results	[168]
[125I]CLINDE	Investigation of the spatial and temporal density of TSPO after excitotoxic lesion	QA (*) 150 nmol in male Wistar rats	1, 7, 14, 60, and 90 days post-injection	• Uptake sign increased in the lesioned striatum from 1 to 60 days • Uptake increase until day 4 and plateau at 4–30 days. • Progressive decrease at 30–90 days	Autoradiography of TSPO expression corresponded to the temporal profile of both microglial activation and astrogliosis. Maximal astrocytic response at 7–14 days and at 14 days for microglia	[172]
[11C]-R-PK11195	Combination of in vivo, ex vivo and IHC approaches to analyse both short- and long-term changes in the QA model	QA (*) 210 nmol in Wistar rats	8, 30 and 60 days post-injection 30 and 60 days post-injection	At 8, 30 and 60 days, [11C]-R-PK11195 binding values are found to be 3.4, 3.0 and 2.8 times higher than those of the control	Reduction of both A2A and dopamine D2 receptors together with an augmentation of microglial activation/macrophage infiltration both in the lesioned striatum and, to some degree, also in extrastriatal areas	[176]
[18F]DPA-714	Pharmacological Characterization of the tracer and evaluation of the cellular contribution to the PET signal	QA (*) 180 nmol in cynomolgus NHP	7, 21, 40 90 days post-injection	• VT : +17%, +54%, +157% and +39% higher than baseline on days 7, 14, 21 and 91. • Decrease of uptake (-73%) in the lesioned striatum after blockage with PK11195	IHC demonstrated progressive microglial activation from day 2 followed by delayed astrocytic reaction reaching maximum between 7 and 14 days. High correlation with in vivo results (r2 = 0.98)	[171]
[18F]PBR06	Evaluation of the feasibility to detect activated microglia in these models	R6/2 , BACHD transgenic mice	Early, mid- and advanced stages	In R6/2 mice (advanced stage): • [18F]PBR06 accumulation in each ROI significantly higher by 25–30% compared with WTs • Reduction of 39–45% of uptake after blocking with PK11195 • Elevated [18F]PBR06 uptake in BACHD mice (early stage) compared with WTs in each ROI	TSPO expression correlated to microglial activation (increased IBA-1) and increased striatal levels of pro-inflammatory cytokines (IL-6 and TNFa)	[187]