Validating noninvasive techniques for 11C‐ER176 PET quantification in controls and Alzheimer’s disease patients

Abstract

AbstractBackgroundNoninvasive yet accurate PET quantification methods are crucial for safe yet meaningful PET studies. [11C]ER176 is a PET radioligand that images neuroinflammation via the 18‐kDa translocator protein (TSPO), which is upregulated in activated microglia and has previously been a PET target in Alzheimer’s disease research. Currently, the gold‐standard method for quantifying ER176 PET is kinetic modeling of the dynamic PET data using the arterial input function (AIF), which is invasive and expensive. The current study explores a pseudo‐reference region (RR) technique to noninvasively quantify ER176 scans to facilitate clinical PET studies.MethodDynamic 90‐min [11C]ER176 PET scans were acquired in 11 participants, 5 controls (5M/0F) and 6 patients (3 MCI‐3M/0F; 3 AD‐2M/1F). Arterial blood data were collected throughout the duration of the scan and were used along with the dynamic imaging data to determine regional total volume of distribution (V T) using the two‐tissue compartment model. Standardized Uptake Value Ratio (SUVR) was calculated by normalizing the radioactivity in each region by that of the reference region (cerebellar gray matter). We explored differences across methods (AIF‐derived V T vs. RR‐derived SUVR) and across groups (controls vs. patients).ResultWithin each group, the outcome measures from AIF and RR methods were well correlated (Controls: R2 = 0.986, p < 0.001; Patients: R2 = 0.983, p < 0.001; Figure 1). Both methods showed greater TSPO expression in patients compared to controls, with mean differences in the medial temporal cortex of 14.99% between groups for V T and 10.65% between groups for SUVR, but lower variance for SUVR compared to V T (Figure 2). Both quantification methods showed similar regional patterns of percent differences between groups, corresponding to tau progression along Braak staging (Figure 3).ConclusionResults suggest that using the cerebellum, which does not accumulate amyloid plaques or tau aggregates until end‐stage disease, as a reference region for [11C]ER176 may be a valid method for quantifying differences between AD patients and controls compared to gold‐standard methodology. Regional increases in neuroinflammation are more reliable for SUVR than V T in AD‐related regions. Ongoing work includes a larger sample size to further validate noninvasive PET quantification.