Non-invasive estimation of [11C]PBR28 binding potential

Martin Schain; Francesca Zanderigo; R Todd Ogden; William C Kreisl

doi:10.1016/j.neuroimage.2017.12.002

Non-invasive estimation of [¹¹C]PBR28 binding potential

Neuroimage. 2018 Apr 1:169:278-285. doi: 10.1016/j.neuroimage.2017.12.002. Epub 2017 Dec 5.

Authors

Martin Schain¹, Francesca Zanderigo², R Todd Ogden³, William C Kreisl⁴

Affiliations

¹ Department of Psychiatry, Columbia University, New York, NY, USA. Electronic address: ms5234@cumc.columbia.edu.
² Department of Psychiatry, Columbia University, New York, NY, USA; Molecular Imaging and Neuropathology Division, New York State Psychiatric Institute, New York, NY, USA.
³ Department of Psychiatry, Columbia University, New York, NY, USA; Molecular Imaging and Neuropathology Division, New York State Psychiatric Institute, New York, NY, USA; Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, NY, USA.
⁴ Molecular Imaging Branch, National Institute of Mental Health, Bethesda, MD, USA; Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY, USA.

PMID: 29203457
DOI: 10.1016/j.neuroimage.2017.12.002

Abstract

[¹¹C]PBR28 is a PET radioligand used to estimate densities of the 18 kDa translocator protein (TSPO) in vivo. Since there is no suitable reference region, arterial blood samples are required for full quantification. Here, we evaluate a methodology for full quantification of [¹¹C]PBR28 PET data that does not require either a reference region or blood samples. Simultaneous estimation (SIME) uses time-activity curves from several brain regions to estimate binding potential (BP_ND), a theoretically more sensitive outcome measure than total distribution volume. SIME can be employed with either a measured arterial input function (AIF) or a template input function (tIF) that has similar shape as the AIF, but with arbitrary amplitude. We evaluated the ability of SIME to detect group differences in TSPO densities using PET and arterial plasma data from 21 Alzheimer's disease (AD) patients and 15 controls that underwent [¹¹C]PBR28 imaging. Regional BP_ND obtained with tIFs were compared to those obtained using measured AIFs. Standard kinetic modeling was also employed for comparison. The sensitivity of each method to detect group differences in TSPO densities were assessed by comparing estimated effect sizes between AD patients and controls. For this purpose, BP_ND estimated for one region with high pathological burden (inferior temporal cortex), and for one region with low pathological burden (cerebellum) was used. BP_ND estimates obtained with SIME and tIFs were close to identical to those obtained with AIF (3.0 ± 21% difference, r² = 0.78). In this dataset, the effect sizes between AD patients and controls for both SIME with AIF and SIME with tIF were similar (30.3%, p = 0.001 and 31.0%, p = 0.004, respectively) and were each greater than the effect size observed using the two-tissue compartment model (16.1%, p = 0.12). None of the tested methods showed difference in TSPO binding in cerebellum. These results demonstrate that BP_ND can be estimated for [¹¹C]PBR28 using SIME, and may be useful in clinical studies. In addition, arterial sampling may not be necessary if tIFs can be reliably estimated.

Keywords: Alzheimer's disease; Kinetic modeling; Neuroinflammation; PET; TSPO; [(11)C]PBR28.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alzheimer Disease / diagnostic imaging*
Alzheimer Disease / metabolism*
Brain / diagnostic imaging*
Brain / metabolism*
Humans
Models, Theoretical*
Positron-Emission Tomography / methods*
Pyrimidines / metabolism*
Pyrimidines / pharmacokinetics
Receptors, GABA / metabolism*

Substances

(methyl-(11)C)N-acetyl-N-(2-methoxybenzyl)-2-phenoxy-5-pyridinamine
Pyrimidines
Receptors, GABA
TSPO protein, human