Radiosynthesis, In Vitro and In Vivo Evaluation of [18F]CBD-2115 as a First-in-Class Radiotracer for Imaging 4R-Tauopathies

• DOI: 10.1021/acschemneuro.0c00801
• Publication Date: 2021-01-26T20:14:11Z
• Authors: Anton Lindberg; Ashley C. Knight; Daniel Sohn; Laszlo Rakos; Junchao Tong; April Radelet; N. Scott Mason; Jeffrey S. Stehouwer; Brian J. Lopresti; William E. Klunk; Johan Sandell; Alexander Sandberg; Per Hammarström; Samuel Svensson; Chester A. Mathis; Neil Vasdev
• Keywords: Radioligand; Radiosynthesis

CBD-2115 was selected from a library of 148 compounds based on pyridinyl-indole scaffold as first-in-class 4R-tau radiotracer. In vitro binding assays showed [3H]CBD-2115 had KD value 6.9 nM and nominal Bmax 500 in expressing P301L transgenic mouse tissue. with human brain tissue homogenates, has higher affinity (4.9 nM) for progressive supranuclear palsy specific deposits than [3H]flortaucipir (45 or [3H]MK-6240 (>50 nM). [18F]CBD-2115 reliably synthesized (3–11% radiochemical yield molar activity 27–111 GBq/μmol >97% purity). Dynamic PET imaging conducted mice, rats, nonhuman primates, all species initial uptake 0.5–0.65 standardized fast clearance normal tissues. could be useful lead radioligand further research 4R-tauopathies, radiotracer development will focus improving affinity.