Dual Time-Point [¹⁸F]Florbetaben PET Delivers Dual Biomarker Information in Mild Cognitive Impairment and Alzheimer’s Disease

Article type: Research Article

Authors: Florek, Lisa^{a; 1} | Tiepolt, Solveig^{a; 1; *} | Schroeter, Matthias L.^c | Berrouschot, Jörg^d | Saur, Dorothee^e | Hesse, Swen^{a; b} | Jochimsen, Thies^a | Luthardt, Julia^a | Sattler, Bernhard^a | Patt, Marianne^a | Hoffmann, Karl-Titus^f | Villringer, Arno^{b; c} | Classen, Joseph^e | Gertz, Hermann-Josef^g | Sabri, Osama^{a; 1} | Barthel, Henryk^{a; 1}

Affiliations: [a] Department of Nuclear Medicine, Leipzig University Hospital, Leipzig, Germany | [b] IFB Adiposity Diseases, Leipzig University Hospital, Leipzig, Germany | [c] Day Clinic for Cognitive Neurology, Leipzig University Hospital & Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany | [d] Department of Neurology, Altenburg Hospital, Germany | [e] Department of Neurology, Leipzig University Hospital, Leipzig, Germany | [f] Department of Neuroradiology, Leipzig University Hospital, Leipzig, Germany | [g] Department of Psychiatry, Leipzig University Hospital, Leipzig, Germany

Correspondence: [*] Correspondence to: Dr. Solveig Tiepolt, MD, Department of Nuclear Medicine, Leipzig University Hospital, Leipzig, Germany. Tel.: +49 341 9718264; Fax: +49 341 9718009; E-mail: solveig.tiepolt@medizin.uni-leipzig.de.

Note: [1] These authors contributed equally to this work.

Abstract: Background:Current research diagnostic criteria for Alzheimer’s disease (AD) and mild cognitive impairment (MCI) due to AD include biomarkers to supplement clinical testing. Recently, we demonstrated that dual time-point [18F]FBB PET is able to deliver both blood flow and amyloid-β (Aβ) load surrogates. Objective:The aim of this study was to investigate whether these surrogates can be utilized as AD biomarkers. Methods:112 subjects (41 with MCI, 50 with probable/possible AD, 21 with other dementias) underwent dual time-point [18F]FBB PET. Data were visually and relative quantitatively (Herholz scores for the early and composite SUVRs for the late PET data) analyzed. Results:In the early images AD-typical patterns were present in 42% /27% /33% of probable/possible AD/MCI/other dementia cases. In late [18F]FBB PET, 42% /29% /38% of probable/possible AD/ MCI/other dementia cases were Aβ-positive. 17% of the MCIs were categorized as “MCI due to AD-high likelihood”, 44% of the probable ADs as “probable AD with high evidence of AD pathophysiological process” and 28% of the possible ADs as “possible AD with evidence of AD pathophysiological process”. 27% of all subjects showed a positive diagnostic and progression biomarker. Herholz scores were lower (0.85±0.05 versus 0.88±0.04, p = 0.015) for probable/possible AD versus MCI. Composite late phase SUVRs were significantly higher (1.65±0.23 versus 1.15±0.17, p < 0.005) in Aβ-positive versus Aβ-negative patients. Herholz and MMSE scores were positively correlated (R = 0.30 p = 0.006). Conclusion:Dual time-point [18F]FBB PET provides dual biomarker information which enables to categorize MCI and AD dementia patients according to established diagnostic criteria. Thus, dual time-point [18F]FBB PET has great potential to supplement diagnostic dementia workups.

Keywords: Alzheimer’s disease, dual biomarker, dual-phase, dual time-point, florbetaben, mild cognitive impairment

DOI: 10.3233/JAD-180522

Journal: Journal of Alzheimer's Disease, vol. 66, no. 3, pp. 1105-1116, 2018