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\begin{document}

\title{Staudinger ligation and fluorine-18: novel~ phosphine-based probes for
in vitro radiolabeling of tumor-infiltrating~ lymphocytes}



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


\vspace{-1em}



  
  \date{April 23, 2024}


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\includegraphics[width=0.70\columnwidth]{figures/CAFACHEM1/CAFACHEM1}

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\textbf{Authors:~ Biti, A.}, Fraguas-S\selectlanguage{ngerman}ánchez, A.I., \& Sarparanta, M.
\textbf{~}

University of Helsinki

\textbf{Background}

Adoptive cell therapy is a promising mode of cancer therapy employing
tumor infiltrating lymphocytes (TILs) with a limited success to
hematologic cancers and melanoma.\textsuperscript{1} Molecular imaging
strategies based on bioorthogonal chemistry and metabolic
glycoengineering for in vivo tracking of TILs provide advantages
compared to conventional techniques.\textsuperscript{2} \textbf{}

\textbf{Aims}

The aim of this study is to develop a new radiolabeling method for TILs
without impairment of their antitumor and homing properties by using a
Staudinger ligation between a perfluoroaryl azide tag\textsuperscript{3}
on the surface of murine OT-I lymphocytes installed by metabolic
glycoengineering and novel fluorine-18 radiolabeled phosphine reagents.

\par\null

\textbf{Methods}

The PFAA-modified D-mannosamine is synthesized according to a reported
procedure. The phosphine reagents present a linker and the NODAGA
radiochelator and are synthesized by using common organic reactions. The
radiolabeling with {[}\textsuperscript{18}F{]}aluminum fluoride (AlF)
requires in situ synthesis of {[}\textsuperscript{18}F{]}AlF starting
from saline-eluted {[}\textsuperscript{18}F{]}fluoride ion and aluminum
chloride (AlCl\textsubscript{3}).

\par\null

\textbf{Results and Conclusion}

This labeling method eliminates the drying step needed for most
{[}\textsuperscript{18}F{]}F\selectlanguage{english}\textsuperscript{-} labeling methods.
Furthermore, Al\textsuperscript{18}F complexes are hydrophilic and can
be used for the radiolabeling of sensitive targets such as cells in
aqueous systems. This could be a method towards the radiolabeling of
TILs without genetic manipulation.

\par\null

\textbf{References}

\textbf{1.} Schietinger, A., et al., Tumor-Specific T Cell Dysfunction
Is a Dynamic Antigen-Driven Differentiation Program Initiated Early
during Tumorigenesis. Immunity, 2016. 45(2): p. 389-401.

\textbf{2.} Rossin, R., et al., Diels--Alder Reaction for Tumor
Pretargeting: In Vivo Chemistry Can Boost Tumor Radiation Dose Compared
with Directly Labeled Antibody. Journal of Nuclear Medicine, 2013.
54(11): p. 1989-1995.

\textbf{3.} Sundhoro, M., et al., Perfluoroaryl Azide Staudinger
Reaction: A Fast and Bioorthogonal Reaction. Angewandte Chemie
International Edition, 2017. 56(40): p. 12117-12121.

\par\null\par\null\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/1/1}
\caption{{Synthesis and radiolabeling of one of the phosphine reagents. The other
compounds present different substituents on the phenyl ring and
different linkers between the phosphine moiety and the NODAGA chelator.
{\label{269056}}%
}}
\end{center}
\end{figure}

~

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\textbf{}

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