Assessment Method for Dynamic Impact of Large Passenger Flow on Urban Rail Transit Network: A Case Study on Chengdu East Railway Station

Large-scale activities, holidays, and emergencies often cause a significantly large burst of passenger flow demand in some urban rail transit (URT) stations in a short time, called large passenger flow (LPF). The LPF will propagate through the entire URT network of the city. The impact of the frequent occurrence of LPF on network service levels is crucial and unpredictable. This article describes an analysis of how this LPF propagates through the entire network inspired by how radionuclide imaging is done in clinical medicine. In this study, with LPF of URT as the research object, a propagation model of LPF in URT based on AFC data, train operation data, and URT network topology data was developed, which was inspired by the concept of radionuclide imaging in clinical medicine. In the condition of obtaining the list of passenger route selection ratios, the dynamic propagation state matrix of the LPF in the network is solved. The contribution value matrix of the LPF was proposed to evaluate the impact of the LPF on the URT network. Considering the LPF in Chengdu East Railway Station, China, as an example, the propagation effect of LPF in the Chengdu Metro network was analyzed, and the effectiveness of the proposed model was confirmed.

Radionuclide imaging of apoptosis for clinical application

Apoptosis was a natural, non-inflammatory, energy-dependent form of programmed cell death (PCD) that can be discovered in a variety of physiological and pathological processes. Based on its characteristic biochemical changes, a great number of apoptosis probes for single-photon emission computed tomography (SPECT) and positron emission tomography (PET) have been developed. Radionuclide imaging with these tracers were potential for the repetitive and selective detection of apoptotic cell death in vivo, without the need for invasive biopsy. In this review, we overviewed molecular mechanism and specific biochemical changes in apoptotic cells and summarized the existing tracers that have been used in clinical trials as well as their potentialities and limitations. Particularly, we highlighted the clinic applications of apoptosis imaging as diagnostic markers, early-response indicators, and prognostic predictors in multiple disease fields.

Radionuclide Imaging of Invasive Fungal Disease in Immunocompromised Hosts

Invasive fungal disease (IFD) leads to increased mortality, morbidity, and costs of treatment in patients with immunosuppressive conditions. The definitive diagnosis of IFD relies on the isolation of the causative fungal agents through microscopy, culture, or nucleic acid testing in tissue samples obtained from the sites of the disease. Biopsy is not always feasible or safe to be undertaken in immunocompromised hosts at risk of IFD. Noninvasive diagnostic techniques are, therefore, needed for the diagnosis and treatment response assessment of IFD. The available techniques that identify fungal-specific antigens in biological samples for diagnosing IFD have variable sensitivity and specificity. They also have limited utility in response assessment. Imaging has, therefore, been applied for the noninvasive detection of IFD. Morphologic imaging with computed tomography (CT) and magnetic resonance imaging (MRI) is the most applied technique. These techniques are neither sufficiently sensitive nor specific for the early diagnosis of IFD. Morphologic changes evaluated by CT and MRI occur later in the disease course and during recovery after successful treatment. These modalities may, therefore, not be ideal for early diagnosis and early response to therapy determination. Radionuclide imaging allows for targeting the host response to pathogenic fungi or specific structures of the pathogen itself. This makes radionuclide imaging techniques suitable for the early diagnosis and treatment response assessment of IFD. In this review, we aimed to discuss the interplay of host immunity, immunosuppression, and the occurrence of IFD. We also discuss the currently available radionuclide probes that have been evaluated in preclinical and clinical studies for their ability to detect IFD.

Affibody Molecule for Positron Emission Tomography Imaging of Human Epidermal Growth Factor Receptor: Validation in Mouse Models and Human Cancer Tissues

Background: Tumor heterogeneity and changes in epidermal growth factor receptor (EGFR) expression status over time post challenges for the design of strategies for effective anti-EGFR monoclonal antibodies in the treatment of non-small-cell lung cancer (NSCLC). Therefore, there is an urgent need to develop techniques for real-time and comprehensive tumor EGFR profiling especially in lung cancer precision medicine trials. Radionuclide imaging of EGFR expression in tumors may screen patients for EGFR-targeting therapies and predict response or resistance to certain treatments.Methods: EGFR-specific Affibody molecule (ZEGFR:1907) was radiolabeled with 68Ga. The radioligands were characterized in vitro and in mice bearing subcutaneous tumors with varying levels of EGFR expression: HCC827 (EGFR overexpression), H1975 (moderate-high), A549 (moderate), H358 (low), and H520 (negative). In vivo tumor targeting activity using PET imaging and biodistribution were conducted in tumor-bearing nude mice. Autoradiography, western blot, immunofluorescence, and immunohistochemistry were performed in human tumor samples. Statistical analyses were performed using GraphPad Prism 7.0. One-way or two-way analysis of variance (ANOVA) followed by the Bonferroni’s multiple comparisons test was used. Statistical significance was set at P < 0.05.Results: 68Ga-NOTA-ZEGFR:1907 showed higher uptake in high EGFR-expressing cells (HCC827, H1975) when compared to cells with moderate to low EGFR (A549, H358) or without EGFR (H520). Radionuclide imaging showed probe accumulation was preferential in EGFR-expressing tumors, particularly in HCC827, H1975 xenografts. A549 and H358 xenografts were mildly and indistinctly visualized. EGFR-negative H520 xenografts were barely visible at any time-point. Biodistribution showed a significantly higher accumulation in HCC827 tumors when compared to H520 tumors (3.20 ± 0.10 %ID/g vs. 0.81 ± 0.08 %ID/g at 2h, P< 0.05). Specific binding to EGFR could be competitively blocked by excess un-radiolabeled affibody molecules in cell uptake, PET imaging and biodistribution assays. Autoradiography showed the regions with high radiotracer uptake partly overlapped with the area of positive EGFR immunofluorescence and immunohistochemistry. Finally, the overall accumulation of autoradiography was positively correlated with immunohistochemistry score.Conclusion: Affibody-based radiotracer 68Ga-NOTA-ZEGFR:1907 is suitable for identification of EGFR expression, showing great potential for further applications and clinical translation.

EANM recommendations based on systematic analysis of small animal radionuclide imaging in inflammatory musculoskeletal diseases

Inflammatory musculoskeletal diseases represent a group of chronic and disabling conditions that evolve from a complex interplay between genetic and environmental factors that cause perturbations in innate and adaptive immune responses. Understanding the pathogenesis of inflammatory musculoskeletal diseases is, to a large extent, derived from preclinical and basic research experiments. In vivo molecular imaging enables us to study molecular targets and to measure biochemical processes non-invasively and longitudinally, providing information on disease processes and potential therapeutic strategies, e.g. efficacy of novel therapeutic interventions, which is of complementary value next to ex vivo (post mortem) histopathological analysis and molecular assays. Remarkably, the large body of preclinical imaging studies in inflammatory musculoskeletal disease is in contrast with the limited reports on molecular imaging in clinical practice and clinical guidelines. Therefore, in this EANM-endorsed position paper, we performed a systematic review of the preclinical studies in inflammatory musculoskeletal diseases that involve radionuclide imaging, with a detailed description of the animal models used. From these reflections, we provide recommendations on what future studies in this field should encompass to facilitate a greater impact of radionuclide imaging techniques on the translation to clinical settings.