Amyloid-β Positron Emission Tomography Imaging Probes: A Critical Review

Article type: Review Article

Authors: Kepe, Vladimir^{a; 1} | Moghbel, Mateen C.^{c; 1} | Långström, Bengt^{d; j; *} | Zaidi, Habib^{e; f} | Vinters, Harry V.^b | Huang, Sung-Cheng^a | Satyamurthy, Nagichettiar^a | Doudet, Doris^g | Mishani, Eyal^h | Cohen, Robert M.ⁱ | Høilund-Carlsen, Poul F.^j | Alavi, Abass^{c; *} | Barrio, Jorge R.^{a; *}

Affiliations: [a] Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA | [b] Department of Pathology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA | [c] Department of Radiology, The Hospital of University of Pennsylvania, Philadelphia, PA, USA | [d] Department of Biochemistry and Organic Chemistry, Uppsala University, Uppsala, Sweden | [e] Division of Nuclear Medicine, Geneva University Hospital, Geneva, Switzerland | [f] Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands | [g] University of British Columbia, Vancouver, BC, Canada | [h] Cyclotron/Radiochemistry Unit/Nuclear Medicine Department, Hadassah Hebrew University Hospital, Jerusalem, Israel | [i] Department of Internal Medicine, Emory University School of Medicine, Atlanta, GA, USA | [j] Department of Nuclear Medicine, Odense University Hospital, University of Southern Denmark, Odense, Denmark

Correspondence: [*] Correspondence to: Jorge R. Barrio, PhD, David Geffen School of Medicine at UCLA, Department of Molecular and Medical Pharmacology, 10833 Le Conte Avenue, CHS B2-086A, Los Angeles, CA 90095-6948, USA. E-mail: [email protected]; Abass Alavi, MD, Department of Radiology, The Hospital of University of Pennsylvania, 423 Guardian Drive, Philadelphia, PA 19104, USA. E-mail: [email protected]; Bengt Långström, PhD, Uppsala University, Department of Biochemistry and Organic Chemistry, Faculty of Technology and Science, Uppsala, Sweden and University of Southern Denmark, Odense University Hospital, Department of Nuclear Medicine, PET & Cyclotron Unit, Institute of Clinical Research Odense, Denmark. E-mail: [email protected].

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

Abstract: The rapidly rising prevalence and cost of Alzheimer's disease in recent decades has made the imaging of amyloid-β deposits the focus of intense research. Several amyloid imaging probes with purported specificity for amyloid-β plaques are currently at various stages of FDA approval. However, a number of factors appear to preclude these probes from clinical utilization. As the available “amyloid specific” positron emission tomography imaging probes have failed to demonstrate diagnostic value and have shown limited utility for monitoring therapeutic interventions in humans, a debate on their significance has emerged. The aim of this review is to identify and discuss critically the scientific issues contributing to the extensive inconsistencies reported in the literature on their purported in vivo amyloid specificity and potential utilization in patients.

Keywords: Amyloid imaging, amyloid ‘specific’ imaging probes, Amyvid, critical review, neuropathologic criteria, PIB, silent medial temporal lobe

DOI: 10.3233/JAD-130485

Journal: Journal of Alzheimer's Disease, vol. 36, no. 4, pp. 613-631, 2013