A simplified radiosynthesis of [18F]MK‐6240 for tau PET imaging

• Published in: Journal of labelled compounds & radiopharmaceuticals Vol. 62; no. 2; pp. 109 - 114
• Main Authors: Hopewell, Robert, Ross, Karen, Kostikov, Alexey, Pascoal, Tharick A., Alberti, Thais, Lacatus‐Samoila, Monica, Soucy, Jean‐Paul, Bennacef, Idriss, Kobayashi, Eliane, Kang, Min Su, Rosa‐Neto, Pedro, Massarweh, Gassan
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01-02-2019
• Subjects: Alzheimer disease; Bombardment; Carbonyls; Chemistry Techniques, Synthetic - instrumentation; Chemistry Techniques, Synthetic - methods; Fluorine isotopes; Fluorine Radioisotopes - chemistry; High-performance liquid chromatography; Imaging; Isoquinolines - chemistry; Mathematical analysis; MK‐6240; Neurofibrillary tangles; NFTs; Positron emission; Positron emission tomography; Positron-Emission Tomography - methods; Purification; Radioactive tracers; Radiochemistry; Radiopharmaceuticals - chemical synthesis; Synthesis; tau; Tau protein; tau Proteins - metabolism; Tomography; MK-6240; tau; NFTs; Alzheimer disease
• ISSN: 0362-4803; 1099-1344
• DOI: 10.1002/jlcr.3695

[18F]MK‐6240 (6‐(fluoro)‐3‐(1H‐pyrrolo[2,3‐c]pyridin‐1‐yl)isoquinolin‐5‐amine) is a highly selective PET radiotracer for the in vivo imaging of neurofibrillary tangles (NFTs). [18F]MK‐6240 was synthesized in one step from its bis‐Boc protected precursor N‐[(tert‐butoxy)carbonyl]‐N‐(6‐nitro‐3‐[1H‐pyrrolo[2,3‐c]pyridin‐1‐yl]isoquinolin‐5‐yl) carbamate in DMSO using [18F] fluoride with TEA HCO3 with step‐wise heating up to 150°C, resulting in an isolated radiochemical yield of 9.8% ± 1.8% (n = 3) calculated from the end of bombardment (5.2% ± 1.0% calculated from the end of synthesis). This new synthetic approach eliminates the acidic deprotection of the bis‐Boc 18F‐labeled intermediate, which reduces the number of operations necessary for the synthesis as well as losses, which occur during deprotection and neutralization of the crude product mixture prior to the HPLC purification. The synthesis was performed automatically with a single‐use cassette on an IBA Synthera+ synthesis module. This synthesis method affords the radioligand with a reliable radiochemical yield, high radiochemical purity, and a high molar activity. [18F]MK‐6240 synthesized with this method has been regularly (n > 60) used in our ongoing human and animal PET imaging studies.
[18F]MK‐6240, a highly selective positron emission tomography (PET) radiotracer for the in vivo imaging of neurofibrillary tangles, was prepared by a simple one‐step reaction and validated for use in humans.