Synthesis and application of targeted molecular imaging agents for enhanced disease imaging and therapy

Abstract

The ultimate success of molecular imaging depends heavily upon discovery of selective imaging probes. This dissertation is focused on development, characterization and in vitro/in vivo imaging of novel imaging agents that target glucose metabolism, translocator protein or cannabinoid CB2 receptor. First conjugable receptor ligands were synthesized, followed by conjugation to signaling moieties. The specific binding of these imaging agents to biologically active targets was then verified by binding studies, in vitro imaging, competition studies and/or in vivo imaging. Most imaging agents developed bind targets specifically with micromolar to nanomolar affinity and were successfully imaged in vitro and/or in vivo.

In addition, one conjugable translocator protein (TSPO) ligand, 6-TSPOmbb732, was coupled to a cancer drug, etoposide, for enhanced cancer therapy. The resulting therapy agent, etoposide-6-TSPOmbb732 (Et6T) seems to protect low TSPO expressing normal cells from off-target effects.