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Get to Know James Inkster: McMaster's Latest Addition to the CCB Department

Updated: Nov 23, 2023



The Department of Chemistry and Chemical Biology here at McMaster University has introduced many fantastic new faculty members over the past few years. This article is going to introduce and highlight the research done by new faculty member James Inkster. Professor Inkster is a radiopharmaceutical chemist whose team will investigate molecular imaging applications where they will both design and test radioactive diagnostic probes.




The Inkster Lab primarily works with fluorine radioligands (18F), and their goal is twofold. Their first objective is to refine and improve the efficiency of known radiosynthetic techniques, and the second is to develop molecular imaging agents for pathologies that currently lack them.


To highlight this first objective, we’re going to dive into one of Dr. Inkster’s most recent papers where he developed a methodology to improve upon a previously reported synthesis of the dopamine receptor agonist [18F]MCL-524. The previous synthesis lacks effectiveness and has poor yield, and so they aimed to design a more efficacious synthesis. This work was inspired by the fact that dopamine receptors are a hallmark of neurological disease, and creating a probe that can measure dopamine receptor activity may help in our understanding of these complex diseases.


Traditionally, when developing syntheses using 18F, anhydrous and basic conditions are used; however, these conditions require additional steps to the synthetic process. In order to work towards developing an efficient and effective method, they aimed to use “non-anhydrous, minimally basic” (NAMB) conditions in order to both eliminate and simplify steps during the synthetic process.


The non-anhydrous aspect was introduced by simply removing the drying process. In recent years, it has been discovered that highly aqueous mediums do not impart the negative aspects once thought. This already simplified the procedure, however, the primary change made was in using a tetraethylammonium eluent in the chromatography column. This eluent is a non-basic compound, and its inclusion is ideal as it prevents the occurrence of carbonate (basic) compounds. In previous literature, they used much more basic eluents which forced them to use protic acids such as HCl (6 M) as deprotection agents later in the synthesis. This is undesirable as it makes the final solution highly acidic, and this high acidity created additional byproducts that required an additional solid-phase extraction during the purification steps.


However, since Inkster et al. managed to mitigate the presence of any basic carbonate compounds, they were able to use a weaker and less reactive Lewis acid (In(OTf)3) in place of a protic one. This caused the reaction solution to be much less acidic and therefore allowed them to bypass the previously necessary solid-phase extraction step.


These modifications allowed them to develop a synthesis that reduced product loss by reducing the number of radiosynthetic steps, and removed a drying step which avoids radioactivity losses due to volatilization of product. Additionally, this method is more compatible with standard cyclotron precursors thus introducing operational simplicity.


When translating this new method into a practiced laboratory technique, Inkster et al. found great success! Despite using non-anhydrous reaction conditions and low precursor masses, they achieved a 18F incorporation rate into the probe of over 50%, which is considered highly successful for this synthesis. Ultimately, this work showcased one aspect of some of the work to come out of the Inkster Lab, and it will be exciting to see what direction his lab goes from there!



The finding of this work has been published in Chemistry: Inkster, J. A. H.; Sromek, A. W..; Akurathi, V.; Neumeyer, J. L.; Packard, A. B. The Non-Anhydrous, Minimally Basic Synthesis of the Dopamine D2 Agonist [18F]MCL-524. Chemistry. 2021, 3 (3), 1047-1056. https://doi.org/10.3390/chemistry3030075







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