Fluorescence imaging has gathered interest over the recent years for its real-time response and high sensitivity. Developing probes for this modality has proven to be a challenge. Quantum dots (QDs) are colloidal nanoparticles that possess unique optical and electronic properties due to quantum confinement effects, whose excellent optical properties make them ideal for fluorescence imaging of biological systems. By selectively controlling the synthetic methodologies it is possible to obtain QDs that emit in the first (650–950 nm) and second (1000–1400 nm) near infra-red (NIR) windows, allowing for superior imaging properties. Despite the excellent optical properties and biocompatibility shown by some NIR QDs, there are still some challenges to overcome to enable there use in clinical applications. In this review, we discuss the latest advances in the application of NIR QDs in preclinical settings, together with the synthetic approaches and material developments that make NIR QDs promising for future biomedical applications.

Over the last twenty-five years 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) has made a significant impact on the field of diagnostic imaging. DOTA is not the only metal chelate in use in medical diagnostics, but it is the only one to significantly impact on all of the major imaging modalities Magnetic Resonance (MR), Positron Emission Tomography (PET), Single Photon Emission Computed Tomography (SPECT), and Fluorescence imaging. This crossover of modalities has been possible due to the versatility of DOTA firstly, to complex a variety of metal ions and secondly, the ease with which it can be modified for different disease states. This has driven research over the last two decades into the chemistry of DOTA and the modification of the substituent pendant arms of this macrocycle to create functional, targeted and dual-modal imaging agents. The primary use of DOTA has been with the lanthanide series of metals, gadolinium for MRI, europium and terbium for fluorescence and neodymium for near infra-red imaging. There are now many research groups dedicated to the use of lanthanides with DOTA although other chelates such as DTPA and NOTA are being increasingly employed. The ease with which DOTA can be conjugated to peptides has given rise to targeted imaging agents seen in the PET, SPECT and radiotherapy fields. These modalities use a variety of radiometals that complex with DOTA, e.g.⁶⁴Cu and ⁶⁸Ga which are used in clinical PET scans, ¹¹¹In, and ⁹⁰Y for SPECT and radiotherapy. In this article, we will demonstrate the remarkable versatility of DOTA, how it has crossed the imaging modality boundaries and how it has been successfully transferred into the clinic.

A key part of the development of metal based Positron Emission Tomography probes is the chelation of the radiometal. In this review the recent developments in the chelation of four positron emitting radiometals, ⁶⁸Ga, ⁶⁴Cu, ⁸⁹Zr and ⁴⁴Sc, are explored. The factors that effect the chelation of each radio metal and the ideal ligand system will be discussed with regards to high in vivo stability, complexation conditions, conjugation to targeting motifs and complexation kinetics. A series of cyclic, cross-bridged and acyclic ligands will be discussed, such as CP256 which forms stable complexes with ⁶⁸Ga under mild conditions and PCB-TE2A which has been shown to form a highly stable complex with ⁶⁴Cu. ⁸⁹Zr and ⁴⁴Sc have seen significant development in recent years with a number of chelates being applied to each metal – eight coordinate di-macrocyclic terephthalamide ligands were found to rapidly produce more stable complexes with ⁸⁹Zr than the widely used DFO.

Smart theranostics are dynamic platforms that integrate multiple functions, including at least imaging, therapy, and responsiveness, in a single agent. This review showcases a variety of responsive theranostic agents developed specifically for magnetic resonance imaging (MRI), due to the privileged position this non-invasive, non-ionising imaging modality continues to hold within the clinical imaging field. Different MRI smart theranostic designs have been devised in the search for more efficient cancer therapy, and improved diagnostic efficiency, through the increase of the local concentration of therapeutic effectors and MRI signal intensity in pathological tissues. This review explores novel small-molecule and nanosized MRI theranostic agents for cancer that exhibit responsiveness to endogenous (change in pH, redox environment, or enzymes) or exogenous (temperature, ultrasound, or light) stimuli. The challenges and obstacles in the design and in vivo application of responsive theranostics are also discussed to guide future research in this interdisciplinary field towards more controllable, efficient, and diagnostically relevant smart theranostics agents.

Alkyne appended lanthanide complexes derived from DO3A undergo copper catalysed cycloaddition reactions with azides to form triazole appended complexes: coordination of one of the triazole nitrogen atoms to the metal centre changes the local coordination environment and the spectroscopic properties of the complex.