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Abstract Colony‐stimulating factor 1 receptor (CSF1R) is highly expressed in mononuclear phagocytes and in the central nervous system. It has emerged as a promising target for tumor therapy and neuroinflammation imaging. Although therapeutic agents targeting CSF1R have shown great success, the development of diagnostic radiotracers for CSF1R has faced numerous challenges. Consequently, there is an urgent need to overcome these obstacles for the development of CSF1R radiotracers, particularly positron emission tomography tracers, not only for diagnostic purposes but also to aid the development of more effective therapeutic drugs. Here, we provide a comprehensive overview of the development of CSF1R radiotracers, presenting detailed profiles of each tracer's ability to image CSF1R. Additionally, we discuss reported CSF1R small‐molecule inhibitors and antibodies, highlighting their relevance to the further development of CSF1R radiotracers. We aim to shed light on the current state of CSF1R radiotracer research and development, provide an insight into the challenges in this field, and offer guidance for future exploration.

Abstract Background The injection activity of tracer, acquisition time, patient-specific photon attenuation, and large body mass, can influence on image quality. Fixed acquisition time and body mass related injection activity in clinical practice results in a large difference in image quality. Thus, this study proposes a patient-specific acquisition time regimen of 68 Ga-DOTATATE total-body positron emission tomography-computed tomography (PET/CT) to counteract the influence of body mass (BM, kg) on image quality, and acquire an acceptable and constant image of patients with neuroendocrine tumors (NETs). Methods The development cohort consisting of 19 consecutive patients with full activity (88.7–204.9 MBq, 2.0 ± 0.1 MBq/kg) was to establish the acquisition time regimen. The liver SNR (signal-to-noise ratio, SNRL) was normalized (SNRnorm) by the product of injected activity (MBq) and acquisition time (min). Fitting of SNRnorm against body mass (BM, kg) in linear correlation was performed. Subjective assessment of image quality was performed using a 5-point Likert scale to determine the acceptable threshold of SNRL, and an optimized acquisition regimen based on BM was proposed, and validated its feasibility through the validation cohort of 57 consecutive NET patients with half activity (66.9 ± 11.3 MBq, 1.0 ± 0.1 MBq/kg) and a fixed acquisition time regimen. Results The linear correlation (R 2 = 0.63) between SNRnorm and BM (kg) was SNRnorm = -0.01*BM + 1.50. The threshold SNRL of acceptable image quality was 11.2. The patient-specific variable acquisition time regimen was determined as: t (min) = 125.4/(injective activity)*(-0.01*BM + 1.50)2. Based on that proposed regimen, the average acquisition time for acceptable image quality in the validation cohort was 2.99 ± 0.91 min, ranging from 2.18 to 6.35 min, which was reduced by 36.50% ~ 78.20% compared with the fixed acquisition time of 10 min. Subjective evaluation showed that acceptable image quality could be obtained at 3.00 min in the validation group, with an average subjective score of 3.44 ± 0.53 (kappa = 0.97, 95% CI: 0.96 ~ 0.98). Bland–Altman analysis revealed good agreement between the proposed regimen and the fixed acquisition time cohort. Conclusion A patient-specific acquisition time regimen was proposed in NET patients in development cohort and validated its feasibility in patients with NETs in validation cohort by 68 Ga-DOTATATE total-body PET/CT imaging. Based on the proposed regimen, the homogenous image quality with optimal acquisition time was available independent of body mass.

The lightning's nature is that different-polarity leaders extend in air. Only negative leaders' development was previously associated to floating plasma. We found that the floating plasma could also lead the positive leader stepwise development.

The positron emission tomography (PET) molecular imaging technology has gained universal value as a critical tool for assessing biological and biochemical processes in living subjects. The favorable chemical, physical, and nuclear characteristics of fluorine-18 (97% β+ decay, 109.8 min half-life, 635 keV positron energy) make it an attractive nuclide for labeling and molecular imaging. It stands that 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) is the most popular PET tracer. Besides that, a significantly abundant proportion of PET probes in clinical use or under development contain a fluorine or fluoroalkyl substituent group. For the reasons given above, 18F-labeled radiotracer design has become a hot topic in radiochemistry and radiopharmaceutics. Over the past decades, we have witnessed a rapid growth in 18F-labeling methods owing to the development of new reagents and catalysts. This review aims to provide an overview of strategies in radiosynthesis of [18F]fluorine-containing moieties with nucleophilic [18F]fluorides since 2015.

Purpose. This study is aimed at investigating the feasibility of cetuximab (Cet) F(ab′)2 fragment- (Cet-F(ab′)2-) based single photon emission tomography/computed tomography (SPECT/CT) for assessing the epidermal growth factor receptor (EGFR) expression in digestive tumor mouse models. Methods. Cet-F(ab′)2 was synthesized using immunoglobulin G-degrading enzyme of Streptococcus pyogenes (IdeS) protease and purified with protein A beads. The product and its in vitro stability in normal saline and 1% bovine serum albumin were analyzed with sodium dodecyl sulfate–polyacrylamide gel electrophoresis. The EGFR expression in the human colon tumor cell line HT29 and the human stomach tumor cell line MGC803 were verified using western blotting and immunocytochemistry. Cet-F(ab′)2 was conjugated with 5(6)-carboxytetramethylrhodamine succinimidyl ester to demonstrate its binding ability to the MGC803 and HT29 cells. Cet-F(ab′)2 was conjugated with NHS-MAG3 for 99mTc radiolabeling. The best imaging time was determined using a biodistribution assay at 1, 4, 16, and 24 h after injection of the 99mTc-MAG3-Cet-F(ab′)2 tracer. Furthermore, 99mTc-MAG3-Cet-F(ab′)2 SPECT/CT was performed on MGC803 and HT29 tumor-bearing nude mice. Results. HT29 cells had low EGFR expression while MGC803 cell exhibited the high EGFR expression. Cet-F(ab′)2 and intact cetuximab showed similar high binding ability to MGC803 cells but not to HT29 cells. Cet-F(ab′)2 and 99mTc-MAG3-Cet-F(ab′)2 showed excellent in vitro stability. The biodistribution assay showed that the target to nontarget ratio was the highest at 16 h (17.29±5.72, n=4) after tracer injection. The 99mTc-MAG3-Cet-F(ab′)2-based SPECT/CT imaging revealed rapid and sustained tracer uptake in MGC803 tumors rather than in HT29 tumors with high image contrast, which was consistent with the results in vitro. Conclusion. SPECT/CT imaging using 99mTc-MAG3-Cet-F(ab′)2 enables the evaluation of the EGFR expression in murine EGFR-positive tumors, indicating the potential utility for noninvasive evaluation of the EGFR expression in tumors.

The discharge current of propagating lightning leaders is critical to understand lightning physics and to design lightning protection systems but almost impossible to be measured directly with present-day technology. In this paper, we have investigated the relationship between luminosity and discharge current of propagating positive leaders in laboratory high voltage atmospheric discharges. The continuously propagating positive leader channels were recorded by high-speed video frames. The brightness distribution of the propagating positive leader channel, which was evaluated by the gray value across the central line, obeyed a normal distribution. The mean grayscale pixel value of the propagating positive leader channel central lines obtained in high-speed video frames was compared with the average discharge current measured in the exposure duration of corresponding frames. There is a statistically significant linearity correlation between the discharge current and the channel luminosity of the propagating positive leader. The result further suggests a potential that the discharge current of propagating positive lightning leaders may be obtained based on the optical information observed in the time domain.

Abstract Radiation therapy of liver cancer is limited by low tolerance of the liver to radiation. Radiosensitizers can effectively reduce the required radiation dose. AGuIX nanoparticles are small, multifunctional gadolinium-based nanoparticles that can carry radioisotopes or fluorescent markers for single-photon emission computed tomography (SPECT), positron emission tomography (PET), fluorescence imaging, and even multimodality imaging. In addition, due to the high atomic number of gadolinium, it can also serve as a tumor radiation sensitizer. It is critical to define the biodistribution and pharmacokinetics of these gadolinium-based nanoparticles to quantitate the magnitude and duration of their retention within the tumor microenvironment during radiotherapy. Therefore, in this study, we successfully labeled AGuIX with 64Cu through the convenient built-in chelator. The biodistribution studies indicated that the radiotracer 64Cu-AGuIX accumulates to high levels in the HepG2 xenograft of nude mice, suggesting that it would be a potential theranostic nanoprobe for image-guided radiotherapy in HCC. We also used a transmission electron microscope to confirm AGuIX uptake in the HepG2 cells. In radiation therapy studies, a decrease in 18F-FDG uptake was observed in the xenografts of the nude mice irradiated with AGuIX, which was injected 1 h before. These results provide proof-of-concept that AGuIX can be used as a theranostic radiosensitizer for PET imaging to guide radiotherapy for liver cancer.

Abstract Atherosclerotic neovascularization plays a significant role in plaque instability as it provides additional lipids and inflammatory mediators to lesions, and resulting in intraplaque hemorrhage. Vascular endothelial growth factor-A (VEGF-A) is considered the predominant proangiogenic factor in angiogenesis. Bevacizumab, a humanized monoclonal antibody, specifically binds to all VEGF-A isoforms with high affinity. Therefore, in this study, we designed 99mTc-MAG3-bevacizumab as a probe, and then investigated its usefulness as a new imaging agent for the detection of plaque neovessels, while also assessing the therapeutic effect of atorvastatin treatment. The ApoE−/− mice treated with atorvastatin were used as the treatment group, and C57BL/6 J mice were selected as the control group. 99mTc-MAG3-bevacizumab uptake was visualized on atherosclerotic lesions by non-invasive in-vivo micro-SPECT/CT and ex-vivo BSGI planar imaging. The value of P/B in each part of the aorta of ApoE−/− mice was higher than in the treatment group and the C57BL/6 J mice, which was confirmed by Oil Red O staining, CD31 staining and VEGF immunohistochemistry staining. 99mTc-MAG3-bevacizumab imaging allowed for the non-invasive diagnosis and assessment of plaque neovascularization. Furthermore, this probe may be used as a new molecular imaging agent to assess the antiangiogenic effect of atorvastatin.

Background: Radiation therapy (RT) of hepatocellular carcinoma (HCC) is limited by low tolerance of the liver to radiation, whereas radiosensitizers are effective in reducing the required radiation dose. Multimodality gadolinium-based nanoparticles (AGuIX) are small and have enhanced permeability and retention effects; thus, they are very suitable for radiation sensitizer HCC RT. Here, we evaluated the potential value of AGuIX for theranostic MRI-radiosensitization in HCC.Methods: The radiosensitization effects of AGuIX were evaluated via in vitro and in vivo experiments. Tumor growth, apoptosis imaging, and immunohistochemistry were performed to verify the antitumor effects of RT with AGuIX.Results:In vitro evaluation of the efficacy of radiosensitivity of the AGuIX demonstrated that the presence of AGuIX significantly decreased HepG2 cell survival when combined with an X-ray beam. In vivo MRI imaging showed the ratio of tumor/liver concentration of the AGuIX was the highest 1 h after intravenous injection. For antitumor effects, we found that the tumor size decreased by RT-only and RT with AGuIX. The antitumor effects were more effective with high-dose AGuIX-mediated RT. Apoptosis imaging and immunohistochemistry both demonstrated that the degree of the cell apoptosis was highest with a high dose of AGuIX-mediated RT.Conclusions: This study provides compelling data that AGuIX can facilitate theranostic MRI-radiosensitization in HCC.

Objective: To investigate the therapeutic efficacy of intratumoral injection of 125I-AA98 mAb for hepatocellular carcinoma (HCC) and its therapy efficacy assessment by 99mTc-HYNIC-duramycin and 99mTc-HYNIC-3PRGD2 SPECT/CT imaging.Methods: HCC xenograft tumor mice models were injected intratumorally with a single dose of normal saline, 10 microcurie (μCi) 125I-AA98 mAb, free 125I, AA98 mAb, 80 μCi 125I-AA98 mAb, and 200 μCi 125I-AA98 mAb. 99mTc-HYNIC-duramycin and 99mTc-HYNIC-3PRGD2 micro-SPECT/CT imaging were performed on days 3 and 7, respectively. The T/M ratio for each imaging was compared with the corresponding immunohistochemical staining at each time point. The relative tumor inhibition rates were documented.Results: In terms of apoptosis, the 200 μCi group demonstrated the highest apoptotic index (11.8 ± 3.8%), and its T/M ratio achieved by 99mTc-HYNIC-duramycin imaging on day 3 was higher than that of the normal saline group, 80 μCi group, 10 μCi group and free 125I group on day 3, respectively (all P < 0.05). On day 3, there was a markedly positive correlation between T/M ratio from 99mTc-HYNIC-duramycin imaging and apoptotic index by TUNEL staining (r = 0.6981; P < 0.05). Moreover, the 200 μCi group showed the lowest T/M ratio on 99mTc-HYNIC-3PRGD2 imaging (1.0 ± 0.5) on day 7 (all P < 0.05) comparing to other groups. The T/M ratio on day 7 was not correlated with integrin ανβ3 staining (P > 0.05). The relative inhibitory rates of tumor on day 14 in the AA98 mAb, 10 μCi, 80 μCi, free 125I, and 200 μCi groups were 26.3, 55.3, 60.5, 66.3, and 69.5%, respectively.Conclusion:125I-AA98 mAb showed more effective apoptosis induced ability for CD146 high expression Hep G2 HCC cells and hold the potential for HCC treatment. Moreover, 99mTc-HYNIC-Duramycin (apoptosis-targeted) imaging and 99mTc-HYNIC-3PRGD2 (angiogenesis-targeted) imaging are reliable non-invasive methods to evaluate the efficacy of targeted treatment of HCC.

To effectively de-noise the Gaussian white noise and periodic narrow-band interference in the background noise of partial discharge ultra-high frequency (PD UHF) signals in field tests, a novel de-noising method, based on a single-channel blind source separation algorithm, is proposed. Compared with traditional methods, the proposed method can effectively de-noise the noise interference, and the distortion of the de-noising PD signal is smaller. Firstly, the PD UHF signal is time-frequency analyzed by S-transform to obtain the number of source signals. Then, the single-channel detected PD signal is converted into multi-channel signals by singular value decomposition (SVD), and background noise is separated from multi-channel PD UHF signals by the joint approximate diagonalization of eigen-matrix method. At last, the source PD signal is estimated and recovered by the l1-norm minimization method. The proposed de-noising method was applied on the simulation test and field test detected signals, and the de-noising performance of the different methods was compared. The simulation and field test results demonstrate the effectiveness and correctness of the proposed method.

OBJECTIVE: This study explores a new, non-invasive imaging method for the specific diagnosis of insulinoma by providing an initial investigation of the use of 125I-labelled molecules of the glucagon-like peptide-1 (GLP-1) analogue liraglutide for in vivo and in vitro small-animal SPECT/CT (single-photon emission computed tomography/computed tomography) imaging of insulinomas. METHODS: Liraglutide was labelled with 125I by the Iodogen method. The labelled 125I-liraglutide compound and insulinoma cells from the INS-1 cell line were then used for in vitro saturation and competitive binding experiments. In addition, in a nude mouse model, the use of 125I-liraglutide for the in vivo small-animal SPECT/CT imaging of insulinomas and the resulting distribution of radioactivity across various organs were examined. RESULTS: The labelling of liraglutide with 125I was successful, yielding a labelling rate of approximately 95% and a radiochemical purity of greater than 95%. For the binding between 125I-liraglutide and the GLP-1 receptor on the surface of INS-1 cells, the equilibrium dissociation constant (Kd) was 128.8 ± 30.4 nmol/L(N = 3), and the half-inhibition concentration (IC50) was 542.4 ± 187.5 nmol/L(N = 3). Small-animal SPECT/CT imaging with 125I-liraglutide indicated that the tumour imaging was clearest at 90 min after the 125I-liraglutide treatment. An examination of the in vivo distribution of radioactivity revealed that at 90 min after the 125I-liraglutide treatment, the target/non-target (T/NT) ratio for tumour and muscle tissue was 4.83 ± 1.30(N = 3). Our study suggested that 125I-liraglutide was predominantly metabolised and cleared by the liver and kidneys. CONCLUSION: The radionuclide 125I-liraglutide can be utilised for the specific imaging of insulinomas, representing a new non-invasive approach for the in vivo diagnosis of insulinomas.

The malignant behaviors of solid tumors such as growth, infiltration and metastasis are mainly nourished by tumor neovascularization. Thus, anti-angiogenic therapy is key to controlling tumor progression. Bevacizumab, a humanized anti-vascular endothelial growth factor (VEGF) antibody, plus chemotherapy or biological therapy can prolong survival for cancer patients, but treatment-related mortality is a concern. To improve inhibitory effect and decrease side-effects on non-small-cell lung cancer (NSCLC), we used Re-188, which is a β emitting radionuclide, directly labeled with bevacizumab for radioimmunotherapy in a human A549 tumor model. Cytotoxic assay data showed that, after 188ReO4− or 188Re-bevacizumab at different concentration for 4 and 24 h, a time- and radioactivity does-dependent reduction in cell viability occurred. Also, an apoptosis assay conformed great apoptosis in the 188Re-bevacizumab group compared with controls and other treatment groups. In vivo, tumor volumes in the 188Re-bevacizumab (11.1 MBq/mice) group were not reduced but growth was delayed compared with other groups. Thus, 188Re-bevacizumab enhanced the therapeutic effect of bevacizumab, suggesting a potential therapeutic strategy for NSCLC treatment.