Nuclear imaging is a powerful non-invasive imaging technique that is rapidly developing in medical theranostics. Nuclear imaging requires radiolabeling isotopes for non-invasive imaging through the radioactive decay emission of the radionuclide. Nuclear imaging probes, commonly known as radiotracers, are radioisotope-labeled small molecules. Nanomaterials have shown potential as nuclear imaging probes for theranostic applications. By modifying the surface of nanomaterials, multifunctional radio-labeled nanomaterials can be obtained for in vivo biodistribution and targeting in initial animal imaging studies. Various surface modification strategies have been developed, and targeting moieties have been attached to the nanomaterials to render biocompatibility and enable specific targeting. Through integration of complementary imaging probes to a single nanoparticulate, multimodal molecular imaging can be performed as images with high sensitivity, resolution, and specificity. In this review, nanomaterial nuclear imaging probes including inorganic nanomaterials such as quantum dots (QDs), organic nanomaterials such as liposomes, and exosomes are summarized. These new developments in nanomaterials are expected to introduce a paradigm shift in nuclear imaging, thereby creating new opportunities for theranostic medical imaging tools.

Quantitative nuclear imaging techniques are in high demand for various disease diagnostics and cancer theranostics. The non-invasive imaging modality requires radiotracing through the radioactive decay emission of the radionuclide. Current preclinical and clinical radiotracers, so-called nuclear imaging probes, are radioisotope-labeled small molecules. Liposomal radiotracers have been rapidly developing as novel nuclear imaging probes. The physicochemical properties and structural characteristics of liposomes have been elucidated to address their long circulation and stability as radiopharmaceuticals. Various radiolabeling methods for synthesizing radionuclides onto liposomes and synthesis strategies have been summarized to render them biocompatible and enable specific targeting. Through a variety of radionuclide labeling methods, radiolabeled liposomes for use as nuclear imaging probes can be obtained for in vivo biodistribution and specific targeting studies. The advantages of radiolabeled liposomes including their use as potential clinical nuclear imaging probes have been highlighted. This review is a comprehensive overview of all recently published liposomal SPECT and PET imaging probes.

Traumatic brain injury (TBI) modelled by lateral fluid percussion-induction (LFPI) in rats is a widely used experimental rodent model to explore and understand the underlying cellular and molecular alterations in the brain caused by TBI in humans. Current improvements in imaging with positron emission tomography (PET) have made it possible to map certain features of TBI-induced cellular and molecular changes equally in humans and animals. The PET imaging technique is an apt supplement to nanotheranostic-based treatment alternatives that are emerging to tackle TBI. The present study aims to investigate whether the two radioligands, [¹¹C]PBR28 and [¹⁸F]flumazenil, are able to accurately quantify in vivo molecular-cellular changes in a rodent TBI-model for two different biochemical targets of the processes. In addition, it serves to observe any palpable variations associated with primary and secondary injury sites, and in the affected versus the contralateral hemispheres. As [¹¹C]PBR28 is a radioligand of the 18 kD translocator protein, the up-regulation of which is coupled to the level of neuroinflammation in the brain, and [¹⁸F]flumazenil is a radioligand for GABA_A-benzodiazepine receptors, whose level mirrors interneuronal activity and eventually cell death, the use of the two radioligands may reveal two critical features of TBI. An up-regulation in the [¹¹C]PBR28 uptake triggered by the LFP in the injured (right) hemisphere was noted on day 14, while the uptake of [¹⁸F]flumazenil was down-regulated on day 14. When comparing the left (contralateral) and right (LFPI) hemispheres, the differences between the two in neuroinflammation were obvious. Our results demonstrate a potential way to measure the molecular alterations in a rodent-based TBI model using PET imaging with [¹¹C]PBR28 and [¹⁸F]flumazenil. These radioligands are promising options that can be eventually used in exploring the complex in vivo pharmacokinetics and delivery mechanisms of nanoparticles in TBI treatment.

Mesenchymal stem/stromal cells (MSCs) are an extensively studied cell type in clinical trials due to their easy availability, substantial ex vivo proliferative capacity, and therapeutic efficacy in numerous pre-clinical animal models of disease. The prevailing understanding suggests that their therapeutic impact is mediated by the secretion of exosomes. Notably, MSC exosomes present several advantages over MSCs as therapeutic agents, due to their non-living nature and smaller size. However, despite their promising therapeutic potential, the clinical translation of MSC exosomes is hindered by an incomplete understanding of their biodistribution after administration. A primary obstacle to this lies in the lack of robust labels that are highly sensitive, capable of directly and easily tagging exosomes with minimal non-specific labeling artifacts, and sensitive traceability with minimal background noise. One potential candidate to address this issue is radioactive iodine. Protocols for iodinating exosomes and tracking radioactive iodine in live imaging are well-established, and their application in determining the biodistribution of exosomes has been reported. Nevertheless, the effects of iodination on the structural or functional activities of exosomes have never been thoroughly examined. In this study, we investigate these effects and report that these iodination methods abrogate CD73 enzymatic activity on MSC exosomes. Consequently, the biodistribution of iodinated exosomes may reflect the biodistribution of denatured exosomes rather than functionally intact ones.