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Purpose: Classical brachytherapy of solid malignant tumors is an invasive procedure which often results in an uneven dose distribution, while requiring surgical removal of sealed radioactive seed sources after a certain period of time. To circumvent these issues, we report the synthesis of intrinsically radiolabeled and gum Arabic glycoprotein functionalized [169Yb]Yb2O3 nanoseeds as a novel nanoscale brachytherapy agent, which could directly be administered via intratumoral injection for tumor therapy. Methods: 169Yb (T½ = 32 days) was produced by neutron irradiation of enriched (15.2% in 168Yb) Yb2O3 target in a nuclear reactor, radiochemically converted to [169Yb]YbCl3 and used for nanoparticle (NP) synthesis. Intrinsically radiolabeled NP were synthesized by controlled hydrolysis of Yb3+ ions in gum Arabic glycoprotein medium. In vivo SPECT/CT imaging, autoradiography, and biodistribution studies were performed after intratumoral injection of radiolabeled NP in B16F10 tumor bearing C57BL/6 mice. Systematic tumor regression studies and histopathological analyses were performed to demonstrate therapeutic efficacy in the same mice model. Results: The nanoformulation was a clear solution having high colloidal and radiochemical stability. Uniform distribution and retention of the radiolabeled nanoformulation in the tumor mass were observed via SPECT/CT imaging and autoradiography studies. In a tumor regression study, tumor growth was significantly arrested with different doses of radiolabeled NP compared to the control and the best treatment effect was observed with ~ 27.8 MBq dose. In histopathological analysis, loss of mitotic cells was apparent in tumor tissue of treated groups, whereas no significant damage in kidney, lungs, and liver tissue morphology was observed. Conclusions: These results hold promise for nanoscale brachytherapy to become a clinically practical treatment modality for unresectable solid cancers. [ABSTRACT FROM AUTHOR]

Radiomics aims to develop novel biomarkers and provide relevant deeper subvisual information about pathology, immunophenotype, and tumor microenvironment. It uses automated or semiautomated quantitative analysis of high‐dimensional images to improve characterization, diagnosis, and prognosis. Recent years have seen a rapid increase in radiomics applications in nuclear medicine, leading to some promising research results in digestive system oncology, which have been driven by big data analysis and the development of artificial intelligence. Although radiomics advances one step further toward the non‐invasive precision medical analysis, it is still a step away from clinical application and faces many challenges. This review article summarizes the available literature on digestive system tumors regarding radiomics in nuclear medicine. First, we describe the workflow and steps involved in radiomics analysis. Subsequently, we discuss the progress in clinical application regarding the utilization of radiomics for distinguishing between various diseases and evaluating their prognosis, and demonstrate how radiomics advances this field. Finally, we offer our viewpoint on how the field can progress by addressing the challenges facing clinical implementation. [ABSTRACT FROM AUTHOR]

The knowledge of interactions among functional proteins helps researchers understand disease mechanisms and design potential strategies for treatment. As a general approach, the fluorescent and affinity tags were employed for exploring this field by labeling the Protein of Interest (POI). However, the autofluorescence and weak binding strength significantly reduce the accuracy and specificity of these tags. Conversely, HaloTag, a novel self-labeling enzyme (SLE) tag, could quickly form a covalent bond with its ligand, enabling fast and specific labeling of POI. These desirable features greatly increase the accuracy and specificity, making the HaloTag a valuable system for various applications ranging from imaging to immobilization of POI. Notably, the HaloTag technique has already been successfully employed in a series of studies with excellent efficiency. In this review, we summarize the development of HaloTag and recent advanced investigations associated with HaloTag, including in vitro imaging (e.g., POI imaging, cellular condition monitoring, microorganism imaging, system development), in vivo imaging, biomolecule immobilization (e.g., POI collection, protein/nuclear acid interaction and protein structure analysis), targeted degradation (e.g., L-AdPROM), and more. We also present a systematic discussion regarding the future direction and challenges of the HaloTag technique. [ABSTRACT FROM AUTHOR]

Gram-negative bacteria have a large variety of channel-forming proteins in their outer membrane, generally referred to as porins. Some display weak voltage dependence. A similar trimeric channel former, named Triplin, displays very steep voltage dependence, rivaling that responsible for the electrical excitability of mammals, and high inter-subunit cooperativity. We report detailed insights into the molecular basis for these very unusual properties explored at the single-molecule level. By using chemical modification to reduce the charge on the voltage sensors, they were shown to be positively charged structures. Trypsin cleavage of the sensor eliminates voltage gating by cleaving the sensor. From asymmetrical addition of these reagents, the positively charged voltage sensors translocate across the membrane and are, thus, responsible energetically for the steep voltage dependence. A mechanism underlying the cooperativity was also identified. Theoretical calculations indicate that the charge on the voltage sensor can explain the rectification of the current flowing through the open pores if it is located near the pore mouth in the open state. All results support the hypothesis that one of the three subunits is oriented in a direction opposite to that of the other two. These properties make Triplin perhaps the most complex pore-forming molecular machine described to date. [ABSTRACT FROM AUTHOR]

Despite the rapid development of immunotherapy, low response rates, poor therapeutic outcomes, and severe side effects still limit its implementation, making the augmentation of immunotherapy an important goal for current research. DNA, which is principally recognized for its functions of encoding genetic information, has recently attracted research interest due to its emerging role in immune modulation. Inspired by the intrinsic DNA‐sensing signaling that triggers the host defense in response to foreign DNA, DNA or nucleic acid‐based immune stimulators have been used in the prevention and treatment of various diseases. Besides that, DNA vaccines allow the synthesis of target proteins in host cells, subsequently inducing recognition of these antigens to provoke immune responses. On this basis, researchers have designed numerous vehicles for DNA and nucleic acid delivery to regulate immune systems. Additionally, DNA nanostructures are also implemented as vaccine delivery systems to elicit strong immune responses against pathogens and diseased cells. This review will introduce the mechanism of harnessing DNA‐mediated immunity for the prevention and treatment of diseases, summarize recent progress, and envisage their future applications and challenges. [ABSTRACT FROM AUTHOR]

In recent years, there have been significant innovations in the development of nanoparticle‐based vaccines and vaccine delivery systems. For the purposes of both design and evaluation, these nanovaccines are imaged using the wealth of understanding established around medical imaging of nanomaterials. An important insight to the advancement of the field of nanovaccines can be given by an analysis of the design rationale of an imaging platform, as well as the significance of the information provided by imaging. Nanovaccine imaging strategies can be categorized by the imaging modality leveraged, but it is also worth understanding the superiority or convenience of a given modality over others in a given context of a particular nanovaccine. The most important imaging modalities in this endeavor are optical imaging including near‐infrared fluorescence imaging (NIRF), emission tomography methods such as positron emission tomography (PET) and single photon emission computed tomography (SPECT) with or without computed tomography (CT) or magnetic resonance (MR), the emerging magnetic particle imaging (MPI), and finally, multimodal applications of imaging which include molecular imaging with magnetic resonance imaging (MRI) and photoacoustic (PA) imaging. One finds that each of these modalities has strengths and weaknesses, but optical and PET imaging tend, in this context, to be currently the most accessible, convenient, and informative modalities. Nevertheless, an important principle is that there is not a one‐size‐fits‐all solution, and that the specific nanovaccine in question must be compatible with a particular imaging modality. This article is categorized under:Nanotechnology Approaches to Biology > Nanoscale Systems in BiologyTherapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic DiseaseTherapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease [ABSTRACT FROM AUTHOR]

Fibroblast activation protein (FAP) is a type II membrane-bound glycoprotein which is overexpressed in cancer-associated fibroblasts and activated fibroblasts at wound healing/inflammatory sites. Since the first clinical application of quinoline-based FAP ligands in 2018, FAP inhibitor (FAPI)-based PET imaging and radiotherapy have been investigated for a wide variety of diseases, both cancerous and non-cancerous. As a consequence, promising strides have been made in particular to improve the understanding of FAPI-based PET imaging and the potential value of FAPI-based tumor radiotherapy. Herein, we present a comprehensive review of radiolabeled FAPI, including their clinical translation, in order to clarify the current and potential future role of this class of molecules in nuclear medicine. In particular, this review underlines the value of FAPI radiopharmaceuticals in the diagnosis or therapy of tumors or benign conditions. However, limitations in present studies have hampered a precise evaluation of FAPI radiopharmaceuticals. Despite this, it will likely be worthwhile to further explore the clinical value of FAPI in diagnosis and therapy through better-designed and larger-population clinical trials in the future. [ABSTRACT FROM AUTHOR]

Simple Summary: The most advanced positron emission tomography–magnetic resonance (PET/MR) combines the high soft tissue contrast of MRI with the high functional/metabolic sensitivity of PET and has the potential to achieve the highest level of diagnostic performance for refractory malignancies in differentiated thyroid cancer (DTC) patients. The utility of PET/MR in the postoperative follow-up of DTC patients has been relatively ambiguous. This retrospective study compared 18F-fluorodeoxyglucose neck PET/MR with PET/CT head-to-head, in order to evaluate the diagnostic efficacy of PET/MR in assessment malignancy in DTC patients after comprehensive treatment. We determined that PET/MR presented better detection rates, image conspicuity, and sensitivity than PET/CT in recurrent DTC lesions and cervical lymph node metastases. The addition of neck PET/MR scan after whole-body PET/CT may provide more favorable diagnostic information. We explored the clinical value of 18F-FDG PET/MR in a head-to-head comparison with PET/CT in loco-regional recurrent and metastatic cervical lymph nodes of differentiated thyroid carcinoma (DTC) patients after comprehensive treatment. 18F-FDG PET/CT and neck PET/MR scans that were performed in DTC patients with suspected recurrence or cervical lymph node metastasis after comprehensive treatment were retrospectively analyzed. Detection rates, diagnostic efficacy, image conspicuity, and measured parameters were compared between 18F-FDG PET/CT and PET/MR. The gold standard was histopathological diagnosis or clinical and imaging follow-up results for more than 6 months. Among the 37 patients enrolled, no suspicious signs of tumor were found in 10 patients, 24 patients had lymph node metastasis, and 3 patients had both recurrence and lymph node metastases. A total of 130 lesions were analyzed, including 3 malignant and 6 benign thyroid nodules, as well as 74 malignant and 47 benign cervical lymph nodes. Compared with PET/CT, PET/MR presented better detection rates (91.5% vs. 80.8%), image conspicuity (2.74 ± 0.60 vs. 1.9 ± 0.50, p < 0.001, especially in complex level II), and sensitivity (80.5% vs. 61.0%). SUVmax differed in benign and malignant lymph nodes in both imaging modalities (p < 0.05). For the same lesion, the SUVmax, SUVmean, and diameters measured by PET/MR and PET/CT were consistent and had significant correlation. In conclusion, compared with 18F-FDG PET/CT, PET/MR was more accurate in determining recurrent and metastatic lesions, both from a patient-based and from a lesion-based perspective. Adding local PET/MR after whole-body PET/CT may be recommended to provide more precise diagnostic information and scope of surgical resection without additional ionizing radiation. Further scaling-up prospective studies and economic benefit analysis are expected. [ABSTRACT FROM AUTHOR]

Simple Summary: Molecular imaging utilizes radionuclides or artificially modified molecules to image particular targets or pathways which are important in the pathogenesis of a certain disease. Transporter-based probes like radioiodine and [18F]fluoro-D-glucose ([18F]FDG) are widely used for diagnosing thyroid cancer (TC) and predicting the prognosis thereafter. However, newly developed probes (peptide, antibody, nanoparticle probes, and aptamer) image the fine molecular changes involved in the pathogenesis of TC and enable target-specific diagnosis and treatment of TC. Furthermore, novel molecular probes have high specificity and sensitivity, imparting a high level of objectivity to the research areas of TC. An essential aspect of thyroid cancer (TC) management is personalized and precision medicine. Functional imaging of TC with radioiodine and [18F]FDG has been frequently used in disease evaluation for several decades now. Recently, advances in molecular imaging have led to the development of novel tracers based on aptamer, peptide, antibody, nanobody, antibody fragment, and nanoparticle platforms. The emerging targets—including HER2, CD54, SHP2, CD33, and more—are promising targets for clinical translation soon. The significance of these tracers may be realized by outlining the way they support the management of TC. The provided examples focus on where preclinical investigations can be translated. Furthermore, advances in the molecular imaging of TC may inspire the development of novel therapeutic or theranostic tracers. In this review, we summarize TC-targeting probes which include transporter-based and immuno-based imaging moieties. We summarize the most recent evidence in this field and outline how these emerging strategies may potentially optimize clinical practice. [ABSTRACT FROM AUTHOR]