Premium
P4‐070: Quantifying translocator protein (TSPO) in Alzheimer's disease and cognitively healthy older persons with 11C‐DPA‐713 PET imaging
Author(s) -
Rosenberg Paul,
Endres Christopher,
Lyketsos Constantine,
Coughlin Jennifer,
Kassiou Michael,
Pomper Martin
Publication year - 2011
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2011.05.2091
Subject(s) - translocator protein , neuroinflammation , positron emission tomography , dementia , medicine , microglia , pittsburgh compound b , pet imaging , nuclear medicine , clinical dementia rating , pathology , disease , inflammation
Background: Neuroinflammation mediated by activated microglia may represent a component of the neurotoxicpathway in Alzheimer’s disease (AD). Our understanding of neuroinflammatory mechanisms as therapeutic targets has been limited by our ability to quantify neuroinflammation in vivo. The translocator protein (TSPO) is a mitochondrial steroid receptor that is markedly upregulatedwhen microglia are activated. [C]DPA-713 is a radiopharmaceutical for positron emission tomography (PET) with highaffinity and specificity for TSPO. Others and we have shown baseline differences in the tissue uptake ofradiopharmaceuticals for TSPO suggesting heterogeneity in the targetconcentration that may or may not be divided into discrete populations, such ashigh and low affinity binders. Thispreliminary report describes [C]DPA-713 PET imaging findings in ADand age-matched, cognitively healthy controls (HCs).Methods: Five HCs (Clinical Dementia Rating 1⁄4 0, mean age 1⁄4 73.4 years) and four participants with mild AD (Clinical Dementia Rating 1⁄4 1.0, mean age 1⁄4 73.25 years) were imaged with [C]DPA-713using the High Resolution Research Tomograph (HRRT). Approximately 20 mCi (370 GBq) of [C]DPA-713was administered by bolus injection followed by imaging. The 60 90 minute standardized uptake values (SUVs) were calculated for 15 regions of interest (ROIs). Results: Two AD participants demonstrated high-affinity [C]DPA-713 uptake, with a mean SUV of 25.9% greater than HCs averaged across all 15 ROIs. TwoAD participants demonstrated low-affinity [C]DPA-713 uptake, with a mean SUV of 35.4% lower than HCs averaged across all 15 ROIs. Conclusions: Our results extend reports of heterogenous affinity of [C]DPA-713 to patients with AD. Since this heterogeneity has been observed with other positron-emitting imaging agents for TSPO, these results suggest that the degree of microglial activationmust be interpretedwith caution when using existing imaging agents with TSPO as a target.