Automated synthesis of PET radiotracers by copperâ mediated 18Fâ fluorination of organoborons: Importance of the order of addition and competing protodeborylation

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142980/1/jlcr3583_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142980/2/jlcr3583.pd

Synthesis and Initial In Vivo Evaluation of [¹¹C]AZ683—A Novel PET Radiotracer for Colony Stimulating Factor 1 Receptor (CSF1R)

Positron emission tomography (PET) imaging of Colony Stimulating Factor 1 Receptor (CSF1R) is a new strategy for quantifying both neuroinflammation and inflammation in the periphery since CSF1R is expressed on microglia and macrophages. AZ683 has high affinity for CSF1R (Ki = 8 nM; IC50 = 6 nM) and >250-fold selectivity over 95 other kinases. In this paper, we report the radiosynthesis of [11C]AZ683 and initial evaluation of its use in CSF1R PET. [11C]AZ683 was synthesized by 11C-methylation of the desmethyl precursor with [11C]MeOTf in 3.0% non-corrected activity yield (based upon [11C]MeOTf), >99% radiochemical purity and high molar activity. Preliminary PET imaging with [11C]AZ683 revealed low brain uptake in rodents and nonhuman primates, suggesting that imaging neuroinflammation could be challenging but that the radiopharmaceutical could still be useful for peripheral imaging of inflammation

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. Results An 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). Conclusion An 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

Engineering Void Space Enclosed within Resorcin[4]arene-Based Supramolecular Frameworks

A family of hydrogen-bonded supramolecular frameworks based on <i>C</i>-alkylresorcinol­[4]­arene (RsC) and 4,4′-bipyridine (bpy) type spacers are described in this article. The size and shape of the void space enclosed within these frameworks are engineered by varying the type of solvent (acetonitrile and ethanol), spacer molecules (4,4′-bipyridine (bpy), <i>trans</i>-1,2-bis­(4-pyridyl)­ethylene (bpe), 1,2-bis­(4-pyridyl)­acetylene (bpa)), and the conformations and/or type of RsC bowl (boat vs cone or <i>C</i>-methylresorcin­[4]­arene/RsC1 vs <i>C</i>-propylresorcin­[4]­arene/RsC3). A change in the solvent system from acetonitrile to ethanol brings about a conformational change with the RsC1 macrocycle and also results in the distinct orientation of spacer molecules around the RsC macrocycle. The predominant feature in all of the frameworks is the O–H···N intermolecular interaction between RsC building blocks and bipyridine-type spacers. The resultant solvent-filled void spaces available within frameworks can be controlled by manipulating the parameters investigated in this study

Copper-Mediated Radiofluorination of Arylstannanes with [¹⁸F]KF

A copper-mediated nucleophilic radiofluorination of aryl- and vinylstannanes with [¹⁸F]­KF is described. This method is fast, uses commercially available reagents, and is compatible with both electron-rich and electron-deficient arene substrates. This method has been applied to the manual synthesis of a variety of clinically relevant radiotracers including protected [¹⁸F]­F-phenylalanine and [¹⁸F]­F-DOPA. In addition, an automated synthesis of [¹⁸F]­MPPF is demonstrated that delivers a clinically validated dose of 200 ± 20 mCi with a high specific activity of 2400 ± 900 Ci/mmol