An updated radiosynthesis of [18F]AV1451 for tau PET imaging

Abstract

Background[18F]AV1451 is a commonly used radiotracer for imaging tau deposits in Alzheimer’s disease (AD) and related non-AD tauopathies. Existing radiosyntheses of [18F]AV1451 require complex purifications to provide doses suitable for use in clinical imaging studies. To address this issue, we have modified the synthesis of [18F]AV1451 to use only 0.5 mg precursor, optimized the Boc-deprotection step and developed a simplified method for HPLC purification of the radiotracer.ResultsAn optimized [18F]AV1451 synthesis using a TRACERLab FXFN module led to high radiochemical yield (202 ± 57 mCi per synthesis) and doses with excellent radiochemical purity (98 ± 1%) and good specific activity (2521 ± 623 Ci/mmol).ConclusionAn updated and operationally simple synthesis of [18F]AV1451 has been developed that is fully automated and prepares radiotracer doses suitable for use in clinical tau PET studies.

High‐yield synthesis of a tau PET radioligand and its nonradioactive ligand using an alternative protection and deprotection strategy

“…Most nonradioactive reference ligands for tau radiopharmaceuticals have poor solubility in both nonpolar and polar organic solvents and thus are obtained in low yields. Moreover, some BOC‐protected nitro precursors undergo thermal deprotection during radiofluorination, and the unprotected nitro precursors give the radiofluorinated products in lower yield than the BOC‐protected precursors due to the decreased solubility 18,20–22 . Therefore, we investigated a high‐yield synthesis of a tau radiopharmaceutical [ 18 F] 1 and its non‐radioactive reference ligand ( 1 ).…”

“…Nonradioactive reference ligands for tau radiopharmaceuticals generally have poor solubility in organic solvents and are thus obtained in low yields. Similarly, 18 F‐labeled tau radiopharmaceuticals are synthesized in higher radiochemical yields from the BOC‐protected nitro precursors than the unprotected precursors because of the increased solubility 18,20–22 . In particular, the RCC to 18 F‐labeled product declines with the progress of the radiofluorination reaction of the BOC‐protected nitro precursor, likely due to the decreased solubility of the precursor resulting from thermal deprotection of the BOC group 22 .…”

“…Similarly, 18 F‐labeled tau radiopharmaceuticals are synthesized in higher radiochemical yields from the BOC‐protected nitro precursors than the unprotected precursors because of the increased solubility 18,20–22 . In particular, the RCC to 18 F‐labeled product declines with the progress of the radiofluorination reaction of the BOC‐protected nitro precursor, likely due to the decreased solubility of the precursor resulting from thermal deprotection of the BOC group 22 . In this study, therefore, we investigated the high‐yield synthesis of 18 F‐RO948 ([ 18 F] 1 ) (Figure 1) and its nonradioactive ligand ( 1 ) for application to the synthesis of other (NH)heteroarene‐based tau imaging radioligands.…”

“In‐loop” 18F‐fluorination: A proof‐of‐concept study

“…This “in‐loop” [ 18 F]fluorination methodology was then applied for the syntheses of [ 18 F]T807 and [ 18 F]FEPPA (Table ). The synthesis of [ 18 F]T807 has previously been reported by several research groups in RCYs ranging from 14% to 32%. [ 18 F]T807 is commonly produced via our two‐step one‐pot procedure, which entails firstly the nucleophilic 18 F‐fluorination of the nitro‐ or tetramethylammonium‐based precursor compound, followed by thermal Boc deprotection to form the desired product.…”

Microfluidic Radiosynthesis of the Muscarinic M2 Imaging Agent [18F]FP-TZTP

“…Currently, the diagnosis of this disease can be achieved through the use of positron emission tomography (PET) using molecules radiolabelled with carbon-11 or fluorine-18, although some of the lead candidates display undesired off-target binding in the brain, which could compromise their utility in molecular imaging. [2] A promising target for the diagnosis of AD involves the muscarinic acetylcholine subtype M 2 receptor, as a selective loss in the cerebral cortex of M 2 receptors over the M 1 subtype receptors has been linked to AD. [3] Therefore, earlier detection of AD through a selective M 2 receptor imaging agent would provide a more favourable prognosis and earlier intervention at presymptomatic stages that could slow disease progression.…”