Studies towards the Ga-68, Cu-64, Zr-89 and In-111 radiolabelling of small molecules and nanoparticles-multimodality PET or SPECT and optical imaging devices

Our recent research interests are towards the development of new multimodal hypoxia imaging agents equipped with fluorescent tags (Figure 1). For this, we have been using flat aromatic tags, which may act as fluorophors (naphthyldiimides), and as near IR fluorescent emitters (naphthyldiimides and perylenes) to act as synthetic scaffolds, which will eventually enable whole body in vivo imaging or blood stability measurements. We have been seeking to develop entirely new dual mode 68Ga‐based, 64Cu‐based, 89Zr‐based and 111In‐based hypoxia imaging agents with extremely high kinetic stability in healthy and cancerous cells (MCF‐7, HeLa, PC3). With the availability of Ge/Ga generators and rapid labelling kinetics, such Ga‐labelled agents would be viable replacements for F‐MISO for PET imaging. A further new concept is the development of potentially trimodal imaging agents (PET/MRI/optical) using filled carbon nanotubes and silica‐encased iron particles functionalised with fluorophores including near IR emitters, CdZnSe2 quantum dots and hypoxia‐targeting vectors. An efficient route towards the radiolabelling of single‐walled carbon nanotubes with 64Cu and 89Zr in aqueous conditions is also described. This route builds on our strategy developed previously, with high yield encapsulation of metallic species in the hydrophobic cavity of the nanotube being discussed.

Studies into the biological effects of all metalloprobes using MTT assays and confocal fluorescence imaging will aid our understanding of their properties and thus help the achievement of added bioimaging benefits. Standard radioanalytical techniques have been used to detect the radiolabelling yield. New synthetic routes to radiolabelled bis(thiosemicarbazones) and nanoparticle‐anchored bis(thiosemicarbazones) are therefore required, and our recent progress in their synthetic methodology involved is described.