September 29, 2023
Reston, VA—A new tau PET radiotracer, 18F-SNFT-1, has been found to be more effective than existing tau PET radiotracers in identifying Alzheimer’s disease in its earliest stages, according to research published in the September issue of The Journal of Nuclear Medicine. In a head-to-head comparison, 18F-SNFT-1 possessed preferable brain pharmacokinetics and demonstrated higher affinity and selectivity for Alzheimer’s tau lesions compared to clinically used second-generation tau PET tracers.
Tau lesions are the neuropathologic hallmarks of Alzheimer’s disease, and tau accumulation is closely associated with future cognitive decline. PET imaging with specific tau radiotracers provides information on the progression of the tau burden, which can help to assess disease activity, determine treatment, and predict therapeutic outcomes.
“Much effort over the past decade has been focused on generating PET radiotracers to visualize tau lesions in vivo,” said Nobuyuki Okamura, MD, PhD, professor of Division of Pharmacology, Faculty of Medicine at Tohoku Medical and Pharmaceutical University in Sendai, Japan. “While progress has been made, existing tau PET radiotracers have problems with insufficient sensitivity to early lesions and the presence of off-target binding. To address these issues, our research team created an optimized tau PET tracer, 18F-SNFT-1, with high sensitivity and specificity to tau pathology in Alzheimer’s disease.”
In the study, researchers compared the binding profile of 18F-SNFT-1 with those of other reported tau PET radiotracers. In vitro binding properties of 18F-labeled tau tracers were evaluated through the autoradiography of frozen human brain tissues from patients with diverse neurodegenerative diseases. Pharmacokinetics, metabolism, and radiation dosimetry were assessed in normal mice after intravenous administration of 18F-SNFT-1.
In vitro binding assays demonstrated that 18F-SNFT-1 possesses high selectivity and high affinity for tau lesions in the brain tissue of patients with Alzheimer’s disease. Autoradiographic analysis of tau deposits in medial temporal brain sections from patients with Alzheimer’s disease showed a higher signal-to-background ratio for 18F-SNFT-1 than for the other tau PET tracers and no significant off-target binding. 18F-SNFT-1 also showed a high initial brain uptake and rapid washout from the brains of normal mice without radiolabeled metabolites.
“Therapeutic agents targeting tau protein are under development, and treatment with anti-tau drugs should be initiated as early as possible,” noted Okamura. “Early detection of tau lesions using 18F-SNFT-1 may accelerate the initiation of therapy with anti-tau drugs and improve the lives of people with Alzheimer’s disease.”
|Figure 3. Tau immunohistochemistry and in vitro autoradiograms of 18F-SNFT-1, 18F-MK-6240, 18F-PM-PBB3, and 18F-flortaucipir in medial temporal sections from cases presenting different Braak stages (AD spectrum). AT8 = anti-phosphorylated tau antibody; CA1 is the region in the hippocampus circuit; FuG = fusiform gyrus; PHG = parahippocampal gyrus; PSP = progressive supranuclear palsy; ROI = region of interest; WM = white matter.|
The authors of “Preclinical Characterization of the Tau PET Tracer [18F]SNFT-1: Comparison of Tau PET Tracers” include Ryuichi Harada, Department of Pharmacology, Tohoku University Graduate School of Medicine, Sendai, Japan, and Division of Brain Science, Department of Aging Research and Geriatric Medicine, Institute of Development, Aging, and Cancer, Tohoku University, Sendai, Japan; Pradith Lerdsirisuk, Yuki Shimizu, Yuka Yokoyama, Yoichi Ishikawa, Ren Iwata, Kazuhiko Yanai, and Shozo Furumoto, Cyclotron and Radioisotope Center, Tohoku University, Sendai, Japan; Yiqing Du, Department of Pharmacology, Tohoku University Graduate School of Medicine, Sendai, Japan; Kaede Kudo, Yasuyuki Taki, Hiroyuki Arai, and Yukitsuka Kudo, Division of Brain Science, Department of Aging Research and Geriatric Medicine, Institute of Development, Aging, and Cancer, Tohoku University, Sendai, Japan; Michinori Ezura and Akio Kikuchi, Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, Japan; Miho Shidahara, Department of Quantum Science and Energy Engineering, Tohoku University, Sendai, Japan; Aiko Ishiki, Division of Brain Science, Department of Aging Research and Geriatric Medicine, Institute of Development, Aging, and Cancer, Tohoku University, Sendai, Japan, and Division of Community Medicine, Tohoku Medical and Pharmaceutical University, Sendai, Japan; Yuya Hatano, Tomohiko Ishihara, and Osamu Onodera, Department of Neurology, Brain Research Institute, Niigata University, Niigata, Japan; Yasushi Iwasaki and Mari Yoshida, Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University, Nagakute, Japan; and Nobuyuki Okamura, Division of Brain Science, Department of Aging Research and Geriatric Medicine, Institute of Development, Aging, and Cancer, Tohoku University, Sendai, Japan, and Division of Pharmacology, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, Sendai, Japan.
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