Nanoparticles have generated a lot of excitement as potential diagnostic and theranostic agents due to their desirable properties such as ease of cargo conjugation (drugs and imaging probes), robust imaging signal, and biocompatibility. This, in combination with multimodal imaging techniques such as Nuclear Imaging, X-ray CT and Optical Imaging (OI), has been an active and growing area of research over the past decade. The MILabs’ SPECT/PET/CT/OI platform, providing high sensitivity and quantitative imaging in any configuration, offers new opportunities in the field of nanomedicine by broadening  our understanding of dynamic nanoparticle distributions and properties in vivo. MILabs’ versatile  4x4D design (four modalities, each with two-, three- and four-dimensional tomographic imaging capabilities) enhances the performance of each imaging modality with the synergistic capabilities offered by an integrated  approach. Several research groups have exploited the unique capabilities of the MILabs’ systems to explore nanotheranostic agents, e.g.:

• Dynamic biodistribution and accumulation of nanoparticles in vivo: the pharmacokinetic profile and biodistribution  of radiolabeled nanoparticles was  visualized and 4D quantified  with MILabs’ SPECT/CT imaging platform, showing superior sensitivity and resolution for characterizing tumor areas in mice as well as favorable biological half-life for translation into the clinic [1,2]. In a different study, the size- and time-dependent circulation half-life and accumulation of polymer nanocarriers were studied [3]. In addition, the biokinetics of ¹¹¹Indium-labelled micelles, as well as the impact of different morphologies on their cellular uptake were visualized using the MILabs’ imaging system. When compared with traditional ex vivo biodistribution studies, a multimodal imaging platform offers the possibility to determine the amount of circulating molecules longitudinally and provides dynamic measurements of localized blood and tumor concentration changes over time [4].

• Novel CT contrast agents: high-performance CT imaging was used to characterize newly developed biodegradable iodine-rich nanopolymersomes and their use as superior contrast agents to commercial iodinated small molecules currently used in the clinic. The  nanopolymersomes have demonstrated several advantages such as excellent stability, small size, high iodine content, and ability to carry tumor-associated peptides which renders these agents as a truly multifunctional system for emerging multimodality nanotheranostics [4]. The versatility of such novel contrast agents can now be enhanced by MILabs’ dynamic dual-energy CT, greatly improving soft-tissue contrast.
   
• Drug delivery: several therapeutic agents are efficient not only when targeting abnormal cells, but also when reaching subcellular compartments. Modular nanotransporters were used to achieve delivery of an Auger electron emitter, ¹¹¹In,  to the nuclei of target cancer cells. Even though it has been widely used as an imaging agent, no therapeutic agent based on ¹¹¹In has yet been developed mainly due to the necessity of its nuclear delivery for efficient cell killing. To this end, the newly synthesized agent was successfully visualized using U-SPECT/CT, showing excellent specificity towards the target of interest [5]. Gold-coated lanthanide phosphate nanoparticles, conjugated to antibodies and labeled with a beta-emitting isotope ¹⁷⁷Lu, were also reported to target metastatic cancer in lungs [6]. By using nanoparticles that contain beta emitters, the authors were able to tailor the treatment of metastatic disease with longer range lower linear-energy transfer radiation, improving the delivery of localized therapy in a more efficient manner. In addition to the nuclear imaging modalities, a large and expanding number of such prototypic nanocarrier materials can now be characterized easily with the recently launched MILabs’ hybrid OI/CT platform, capable of 3D fluorescence tomography (FLT) and bioluminescence tomography (BLT) in a highly sensitive and quantitative manner.