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\begin{document}

\title{Development of a Carbon-11~ Positron Emission Tomography Pro-Radiotracer
for Imaging the Astroglial~ Glutamate Transporter 1}



\author[1]{SRSTT Radiopharmaconnect}%
\affil[1]{Radiopharmaconnect}%


\vspace{-1em}



  
  \date{May 26, 2024}


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\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/CAFACHEM1/CAFACHEM1}

\end{center}
\end{figure}

\href{https://www.srsweb.org/cafachem2020}{\textbf{CAFACHEM~2020}}
\textbf{} organizers are grateful for the support of
\textbf{\href{www.gehealthcare.co.uk/products/molecular-imaging/pet-radiopharmacy/chemistry--systems}{}\href{https://www.gehealthcare.co.uk/products/molecular-imaging/pet-radiopharmacy/chemistry--systems}{GE
Healthcare}}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/GE-Healthcare-PET-Chemistry-Systems-Banner---CAFACHEM/GE-Healthcare-PET-Chemistry-Systems-Banner---CAFACHEM}

\end{center}
\end{figure}

\par\null

\textbf{Authors: Igor Camargo Fontana\textsuperscript{1,\textbf{3}}},
Salvatore Bongarzone\textsuperscript{1,2}, Eduardo
Zimmer\textsuperscript{3}, Diogo Onofre de Souza\textsuperscript{3},
Antony Gee\textsuperscript{1,2} \textbf{}

\textsuperscript{1}Division of Imaging Sciences and Biomedical
Engineering, King's College London, 4\textsuperscript{th} Floor, Lambeth
Wing, St Thomas' Hospital, London SE1 7EH, United Kingdom.

\textsuperscript{2}PET Imaging Centre Facility, St Thomas' Hospital,
London SE1 7EH, United Kingdom.

\textsuperscript{3}Department of Biochemistry, Universidade Federal do
Rio Grande do Sul, Porto Alegre, \textbf{} Brazil.

\par\null

\textbf{Background}

Astrocyte glutamate transporter 1 (GLT-1) dysfunction is implicated in
several neurodegenerative diseases\textsuperscript{1}. Selective GLT-1
inhibitors\textsuperscript{2} bear a carboxylic acid which would lead to
low brain penetrance. PET imaging would allow to study the in vivo brain
penetration of carboxylic acid and their derivatives (e.g. esters).

\par\null

\textbf{Aims}

The aim of this work is to develop the carbon-11 labelled
pro-radiotracer ({[}\textsuperscript{11}C{]}IF1) which we hypothesize
will be hydrolysed to the GLT-1-targeting radiotracer
({[}\textsuperscript{11}C{]}IF2 -- Fig 1B) after passage across the BBB
(Fig 1C).

\par\null

\textbf{Methods}

Eckert \& Ziegler Modular-Lab system was implemented for
{[}\textsuperscript{11}C{]}IF1 radiosynthesis.
{[}\textsuperscript{11}C{]}CO\textsubscript{2} to
{[}\textsuperscript{11}C{]}CO conversion followed the silane lithium
derivative strategy\textsuperscript{3}. The
{[}\textsuperscript{11}C{]}CO afforded {[}\textsuperscript{11}C{]}IF0
via a palladium-mediated {[}\textsuperscript{11}C{]}carbonylation
reaction (Fig 1D). {[}\textsuperscript{11}C{]}IF1 was obtained after BOC
deprotection with trifluoroacetic acid (90 \selectlanguage{english}C, 4 min).

\par\null

\textbf{Results and Conclusion}

Crude {[}\textsuperscript{11}C{]}IF1 was obtained within 18 min after
the end of bombardment with radiochemical yield of 8\% (decay corrected)
based on radio-HPLC, with a radiochemical purity of 99\% after
reformulation. {[}\textsuperscript{11}C{]}IF1, a potential GLT-1
pro-radiotracer, was successfully synthesized from
{[}\textsuperscript{11}C{]}CO. Low brain uptake was observed in mouse
receiving {[}\textsuperscript{11}C{]}IF1 intravenously.

\par\null

\textbf{References}

\textbf{1.} Peterson AR.~\emph{et al.} Post-translational Regulation of
GLT-1 in Neurological Diseases and Its Potential as an Effective
Therapeutic Target.~\emph{Front Mol Neurosci.~}2019;12(164).

\textbf{2.}~Greenfield A.~\emph{et al.} Synthesis and biological
activities of aryl-ether-, biaryl-, and fluorene-aspartic acid and
diaminopropionic acid analogs as potent inhibitors of the high-affinity
glutamate transporter EAAT-2.~\emph{Bioorg Med Chem Lett}. 2005;15(22).

\textbf{3.} Taddei C. \emph{et al}. {[}(11)C{]}CO2 to {[}(11)C{]}CO
conversion mediated by {[}(11)C{]}silanes: a novel route for
{[}(11)C{]}carbonylation reactions. \emph{Chem Commun (Camb)}.
2015;51(59).

\par\null\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/6-fontana/6-fontana}

\end{center}
\end{figure}

\textbf{Legend:}

\textbf{{[}A{]}} GLT-1 specific inhibitor developed by Greenfield et al.
(2005). \textbf{{[}B{]}} EAAT2-specific radiotracer -
{[}\textsuperscript{11}C{]}IF2. \textbf{{[}C{]}} Hypothesis of work: the
pro-radiotracer {[}\textsuperscript{11}C{]}IF1 is~ hydrolysed, releasing
inside the brain the EAAT2-specific radiotracer
{[}\textsuperscript{11}C{]}IF2. \textbf{{[}D{]}} Radiosynthesis scheme
to obtain the pro-radiotracer {[}\textsuperscript{11}C{]}IF1\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/CAFACHEM/CAFACHEM}

\end{center}
\end{figure}

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\end{document}

