Synthesis and Structure–Affinity Relationship of Small Molecules for Imaging Human CD80 by Positron Emission Tomography

The costimulatory molecule CD80 is
an early marker for immune activation.
It is upregulated on activated antigen-presenting cells. We aimed
at developing a tracer for imaging CD80 by positron emission tomography
(PET). Novel CD80 ligands were synthesized and tested by SPR for affinity
to human CD80 (hCD80) and displacement of endogenous ligands. Several
compounds bound with one-digit nanomolar affinity to hCD80 and displaced
CTLA-4 and CD28 at nanomolar concentrations. A structure–affinity
relationship study revealed relevant moieties for strong affinity
to hCD80 and positions for further modifications. Lead compound MT107
(7f) was radiolabeled with carbon-11. In vitro, [11C]­MT107 showed specific binding to hCD80-positive tissue
and high plasma protein binding. In vivo, [11C]­MT107 accumulated
in liver, gall bladder, and intestines but only scarcely in hCD80-positive
xenografts. The unfavorable in vivo performance may result from high
plasma protein binding and extensive biliary excretion.