Development of Novel Macrophage Imaging Agents
Macrophages are an important class of cell involved in host defence and homeostasis that are able to alter their phenotype in response to their surroundings and affect a wide range of biological processes. These properties make them critical to host function in normal and disease settings, leading to their utility as targets to inform upon functional status of an organ/tissue as well as for therapeutic intervention. Thus the development of macrophage-specific imaging agents has potential clinical applications in the diagnosis and measuring response to treatment of disease. This thesis sets forth the development of novel antibody-based nuclear imaging agents 99mTc-SER4, 64Cu-NOTA-SER4, and 99mTc-ED3 targeting the antigen sialoadhesin and 1111n-DTPA-ED2 targeting CD163, of which both antigens are macrophage-restricted. All the agents described herein exhibit tracking to endogenous sialoadhesin-expressing macrophage populations with exceptionally fast blood clearance times. In a heterotopic cardiac transplantation model of acute rejection the tracer 99mTc-SER4 demonstrated enhanced targeting to the rejected organ, whilst following recovery to localised bone marrow radioablation preliminary data showed increased 64Cu-NOTA­SER4 in the ablated bone marrow. The tracers 1111n-DTPA-ED2 and 99mTc-ED3 also demonstrated the feasibility of imaging distinct macrophage populations simultaneously. In this thesis, we present sialoadhesin as a candidate target for the imaging of macrophage populations in vivo, with the potential for translation into the clinic.
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