Modulation transfer function of implantable phakic intraocular contact lens (IPCL) for myopia and presbyopia.

PURPOSE: This study aimed to assess the optical quality of myopic and presbyopic IPCLs with different additional powers, and to investigate the effects of pupil size on the optical quality of these IPCLs using an in-vitro modulation transfer function (MTF) measurement system. METHODS: Linear scatter functions (LSFs) were recorded using the OPAL Vector system and an eye phantom consisting of wet cells filled with a balanced salt solution. A myopic IPCL or a presbyopic IPCL was placed in the posterior chamber of this model. The MTF was calculated from the LSF using the fast Fourier transform techniques. The effective apertures were set at 2.0 to 5.0 mm in 1.0 mm steps. RESULTS: The in-focus MTF values of the myopic IPCL and presbyopic IPCL with additional powers of + 2.0 and + 4.0 diopters at 100 cycles/mm for an effective aperture of 3.0 mm were 43%, 27%, and 24%, respectively. The in-focus MTF value of both myopic and presbyopic IPCLs was the highest when the effective aperture was set at 3.0 mm, and it gradually worsened when the effective aperture became larger than 3.0 mm at 20, 60, and 100 cycles/mm. CONCLUSIONS: Both myopic and presbyopic IPCLs provided excellent MTF values, but the additional power profile can deteriorate optical performance in presbyopic IPCL-implanted eyes, even with a low additional power. Pupil size can influence visual quality in IPCL-implanted eyes for both myopia and presbyopia.

EDB-FN targeted probes for the surgical navigation, radionuclide imaging, and therapy of thyroid cancer.

PURPOSE: Extradomain B of fibronectin (EDB-FN) is a promising diagnostic and therapeutic biomarker for thyroid cancer (TC). Here, we identified a high-affinity EDB-FN targeted peptide named EDBp (AVRTSAD) and developed three EDBp-based probes, Cy5-PEG4-EDBp(Cy5-EDBp), [18F]-NOTA-PEG4-EDBp([18F]-EDBp), and [177Lu]-DOTA-PEG4-EDBp ([177Lu]-EDBp), for the surgical navigation, radionuclide imaging, and therapy of TC. METHODS: Based on the previously identified EDB-FN targeted peptide ZD2, the optimized EDB-FN targeted peptide EDBp was identified by using the alanine scan strategy. Three EDBp-based probes, Cy5-EDBp, [18F]-EDBp, and [177Lu]-EDBp, were developed for fluorescence imaging, positron emission tomography (PET) imaging, and radiotherapy in TC tumor-bearing mice, respectively. Additionally, [18F]-EDBp was evaluated in two TC patients. RESULTS: The binding affinity of EDBp to the EDB fragment protein (Kd = 14.4 ± 1.4 nM, n = 3) was approximately 336-fold greater than that of the ZD2 (Kd = 4839.7 ± 361.7 nM, n = 3). Fluorescence imaging with Cy5-EDBp facilitated the complete removal of TC tumors. [18F]-EDBp PET imaging clearly delineated TC tumors, with high tumor uptake (16.43 ± 1.008%ID/g, n = 6, at 1-h postinjection). Radiotherapy with [177Lu]-EDBp inhibited tumor growth and prolonged survival in TC tumor-bearing mice (survival time of different treatment groups: saline vs. EDBp vs. ABRAXANE vs. [177Lu]-EDBp = 8.00 d vs. 8.00 d vs. 11.67 d vs. 22.33 d, ***p < 0.001). Importantly, the first-in-human evaluation of [18F]-EDBp demonstrated that it had specific targeting properties (SUVmax value of 3.6) and safety. CONCLUSION: Cy5-EDBp, [18F]-EDBp, and [177Lu]-EDBp are promising candidates for the surgical navigation, radionuclide imaging, and radionuclide therapy of TC, respectively.

A novel PSMA targeted dual-function near-infrared fluorescence and PET probe for the image-guided surgery and detection of prostate cancer.

PURPOSE: Prostate-specific membrane antigen (PSMA) is a promising diagnostic biomarker for prostate cancer (PCa). NYM016, a novel small-molecule PSMA-targeted fluorescence probe for the surgical navigation of PCa, was designed in this work. Furthermore, the potential of the PET agent [68Ga]Ga-NYM016 for the radionuclide imaging of PCa was evaluated. METHODS: NYM016 was designed with the near-infrared fluorescent group Cyanine 7 (Cy7) and the chelating group NOTA. The radioactive probe [68Ga]Ga-NYM016 was designed and synthesized on the basis of NYM016. The abovementioned probes were assessed in PSMA-positive xenograft-bearing models and patients diagnosed with PCa. RESULTS: NYM016 obviously aggregated in the tumor site of the mouse model, and its fluorescence intensity was stable within 24 h. NYM016 was well-tolerated, and no adverse events were found in the clinical study. Moreover, it was also observed in the excised lesions from the patient with PCa, and its fluorescence aggregated at the same site where PSMA was highly expressed. In addition, the PSMA xenograft demonstrated intense [68Ga]Ga-NYM016 uptake at 2.5 min after injection. At 3 h after injection, [68Ga]Ga-NYM016 uptake by the PSMA xenograft gradually increased to 6.40 ± 0.19%ID/g, which was higher that by the blocked and negative groups (2.28 ± 0.07%ID/g, P < 0.05; 2.28 ± 0.22%ID/g, P < 0.05). In the clinical study, [68Ga]Ga-NYM016 was well-tolerated and no adverse events were observed. Substantial accumulation was observed in primary and metastatic lesions in a patient with recurrence with the maximum standardized uptake value of 18.93. Meanwhile, negative [68Ga]Ga-NYM016 uptake was observed at the prostate site of a patient with prostatitis. CONCLUSION: The novel fluorescence probe NYM016 and the radioactive tracer [68Ga]Ga-NYM016 are promising candidates for the surgical navigation and radionuclide imaging of PCa, respectively. TRIAL REGISTRATION: The clinical evaluation of this study was registered at Clinicaltrial.gov (NCT05623878) on 21 Dec, 2022.

Automated Synthesis and Preclinical Evaluation of Optimized Integrin α6-Targeted Positron Emission Tomography Imaging of Pancreatic Cancer.

Integrin α6 has been considered a promising biomarker, is overexpressed in many tumors, and plays a vital role in tumor formation, recurrence, and metastasis. In this study, we identified a novel high-affinity integrin α6-targeted peptide named RD2 (Arg-Trp-Tyr-Asp-PEG4)2-Lys-Lys and developed a 18F-radiolabeled peptide tracer ([18F]-AlF-NOTA-RD2) and evaluated its potential application in positron emission tomography (PET) imaging of pancreatic cancer. [18F]-AlF-NOTA-RD2 was produced using GMP (Good Manufacturing Practice of Medical Products)-compliant automatic radiosynthesis on a single GE FASTLab2 cassette-type synthesis module. The stability of [18F]-AlF-NOTA-RD2 was analyzed in phosphate-buffered saline (PBS) and fetal bovine serum (FBS). The cell uptake assay of the tracer was assessed using PANC-1 cells. In addition, small-animal PET imaging and biodistribution studies of [18F]-AlF-NOTA-RD2 were performed in pancreatic cancer subcutaneous tumor-bearing mice. The PET tracer [18F]-AlF-NOTA-RD2 was obtained with a radiochemical yield of 23.7 ± 4.7%, radiochemical purity of >99%, and molar activity of 165.7 ± 59.1 GBq/µmol. [18F]-AlF-NOTA-RD2 exhibited good in vitro stability in PBS and FBS. LogP octanol water value for the tracer was -2.28 ± 0.05 (n = 3). The binding affinity of RD2 to the integrin α6 protein (Kd = 0.13 ± 3.65 µM, n = 3) was significantly higher than that of the RWY (CRWYDENAC) (Kd = 6.97 ± 1.44 µM, n = 3). Small-animal PET imaging and biodistribution also revealed that [18F]-AlF-NOTA-RD2 displayed rapid and good tumor uptake and lower liver background uptake in PANC-1 tumor-bearing mice. [18F]-AlF-NOTA-RD2 showed significant radioactivity accumulation in tumors and was successfully blocked by NOTA-RD2. Compared with [18F]-FDG, [18F]-AlF-NOTA-RD2 PET imaging and biodistribution studies in PANC-1 xenograft tumor-bearing mice confirmed a good tumor-to-muscle ratio (8.69 ± 2.03 vs 1.41 ± 0.23, respectively) at 0.5 h and (2.99 ± 3.02 vs 1.43 ± 0.17, respectively) at 1 h post injection. Autoradiography of human pancreatic cancer tumor tissues further confirmed high accumulation of [18F]-AlF-NOTA-RD2. In summary, we developed an optimized integrin α6-targeted imaging tracer and obtained high radioactivity products with a cassette-type synthesis module; moreover, the tracer exhibited good binding affinity with integrin α6 and good target specificity for PANC-1 cells in xenograft pancreatic tumor-bearing mice, demonstrating its promising application as a noninvasive PET radiotracer of integrin α6 expression in pancreatic cancer.

Assessment of androgen receptor expression in breast cancer patients using 18 F-FDG PET/CT radiomics and clinicopathological characteristics.

OBJECTIVE: In the present study, we mainly aimed to predict the expression of androgen receptor (AR) in breast cancer (BC) patients by combing radiomic features and clinicopathological factors in a non-invasive machine learning way. MATERIALS AND METHODS: A total of 48 BC patients, who were initially diagnosed by 18F-FDG PET/CT, were retrospectively enrolled in this study. LIFEx software was used to extract radiomic features based on PET and CT data. The most useful predictive features were selected by the LASSO (least absolute shrinkage and selection operator) regression and t-test. Radiomic signatures and clinicopathologic characteristics were incorporated to develop a prediction model using multivariable logistic regression analysis. The receiver operating characteristic (ROC) curve, Hosmer-Lemeshow (H-L) test, and decision curve analysis (DCA) were conducted to assess the predictive efficiency of the model. RESULTS: In the univariate analysis, the metabolic tumor volume (MTV) was significantly correlated with the expression of AR in BC patients (p < 0.05). However, there only existed feeble correlations between estrogen receptor (ER), progesterone receptor (PR), and AR status (p = 0.127, p = 0.061, respectively). Based on the binary logistic regression method, MTV, SHAPE_SphericityCT (CT Sphericity from SHAPE), and GLCM_ContrastCT (CT Contrast from grey-level co-occurrence matrix) were included in the prediction model for AR expression. Among them, GLCM_ContrastCT was an independent predictor of AR status (OR = 9.00, p = 0.018). The area under the curve (AUC) of ROC in this model was 0.832. The p-value of the H-L test was beyond 0.05. CONCLUSIONS: A prediction model combining radiomic features and clinicopathological characteristics could be a promising approach to predict the expression of AR and noninvasively screen the BC patients who could benefit from anti-AR regimens.

Exploration of bacterial community-induced polycyclic aromatic hydrocarbons degradation and humus formation during co-composting of cow manure waste combined with contaminated soil.

To solve polycyclic aromatic hydrocarbons (PAHs) pollution, composting was chosen as a remediation method. During composting, the dissipation of PAHs was carried out by resource utilization of organic solid waste and its degradation by bacteria. This study was conducted by co-composting with contaminated soil and cow manure. The results showed that the degradation rates of naphthalene (Nap), phenanthrene (Phe), and benzo[α]pyrene (BaP) could reach 82.2%, 79.4%, and 59.6% respectively during composting. Cluster analysis indicated that polyphenol oxidase (PPO), laccase, and protease were important drivers of PAHs transformation. The content of humic substances (HS) was 106.67 g/kg in PAH treatment, which was significantly higher than that in the control group at 65 days. The phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) and network analysis was used to infer the degradation mechanism of PAHs by microorganisms. The degradation of PAHs by PPO was found to have a significant contribution to the formation of HS. It was shown that PAHs and metabolic intermediates were more inclined to be oxidized and decomposed by PPO to form quinone, which in turn condensed with amino acids to form HS. Composting could promote the degradation of PAHs while improving the quality of compost, achieving a win-win situation.

Identify the potential driving mechanism of reconstructed bacterial community in reduce CO2 emissions and promote humus formation during cow manure composting.

The mineralization of organic components releases CO2 during composting, which not only leads to the loss of organic carbon, but has a direct negative impact on the environment. Malonic acid as a competitive inhibitor of succinate dehydrogenase could affect the tricarboxylic acid (TCA) cycle and reduce CO2 emissions. However, the bacterial interaction and organic component transformation has less known how to malonic acid reduce CO2 and improve of humus synthesis in complex composting. The aim of this study was to investigated the malonic acid on organic carbon sequestration and transforming cow manure waste into products with high humus content. Humus content was elevated by 16.8% and cumulative CO2 emissions (30 d)d reduced by 13.6% after malonic acid addition compared to the CK. SparCC analysis of bacterial interaction presented that the network complexity and stability was more higher with malonic acid addition, while a greater concentration of keystones and their ecological metabolic functions was observed, suggesting they weaken the influence of TCA cycle inhibition by enhancing interactions. PICRUSt predictions indicate that malonic acid might enhance humus content by promoting the synthesis of polyphenols and polymerization with amino acids. This study investigated the potential mechanism of regulators to enhance quality and reduce emissions during humification process, providing a new strategy for the resource utilization of organic solid waste.

The efficacy and safety of Iodine-131-metaiodobenzylguanidine therapy in patients with neuroblastoma: a meta-analysis.

OBJECTIVE: Neuroblastoma is a common extracranial solid tumor of childhood. Recently, multiple treatments have been practiced including Iodine-131-metaiodobenzylguanidine radiation (131I-MIBG) therapy. However, the outcomes of efficacy and safety vary greatly among different studies. The aim of this meta-analysis is to evaluate the efficacy and safety of 131I-MIBG in the treatment of neuroblastoma and to provide evidence and hints for clinical decision-making. METHODS: Medline, EMBASE database and the Cochrane Library were searched for relevant studies. Eligible studies utilizing 131I-MIBG in the treatment of neuroblastoma were included. The pooled outcomes (response rates, adverse events rates, survival rates) were calculated using either a random-effects model or a fixed-effects model considering of the heterogeneity. RESULTS: A total of 26 clinical trials including 883 patients were analyzed. The pooled rates of objective response, stable disease, progressive disease, and minor response of 131I-MIBG monotherapy were 39%, 31%, 22% and 15%, respectively. The pooled objective response rate of 131I-MIBG in combination with other therapies was 28%. The pooled 1-year survival and 5-year survival rates were 64% and 32%. The pooled occurrence rates of thrombocytopenia and neutropenia in MIBG monotherapy studies were 53% and 58%. In the studies of 131I-MIBG combined with other therapies, the pooled occurrence rates of thrombocytopenia and neutropenia were 79% and 78%. CONCLUSION: 131I-MIBG treatment alone or in combination of other therapies is effective on clinical outcomes in the treatment of neuroblastoma, individualized 131I-MIBG is recommended on a clinical basis.

Diagnostic Performance of [18F]-Labeled PET/CT Tracers for Lymph Node/Bone Metastasis and Biochemical Recurrence Detection in Advanced Prostate Cancer: A Meta-Analysis.

PURPOSE: The aim of this study was to explore the diagnostic value of different fluorine-18 (18F)-labeled tracers for lymph node/bone metastasis and biochemical recurrence detection in advanced prostate cancer (PCa). METHODS: PubMed, Embase, Web of Science, Cochrane databases, and the WHO International Clinical Trial Center were searched. The inclusion criteria were determined based on the Preferred Report Items of the Systematic Review and Meta-Analysis Guidelines. The Quality Assessment of Diagnostic Accuracy Studies-2 was used to assess the quality assessment of the included studies. The quantitative analysis of the included literature was performed on the patient and lesion basis, and the equivocal findings were considered negative or positive results, respectively. RESULTS: Thirty-seven articles were included. On the patient basis, the pooled sensitivity and specificity of [18F]-labeled tracers were 0.80 (95% confidence interval [CI]: 0.78-0.83) and 0.89 (95% CI: 0.87-0.90) when equivocal results were considered to be positive and 0.80 (95% CI: 0.77-0.82) and 0.87 (95% CI: 0.85-0.89) when equivocal results were considered to be negative. On the lesion basis, the pooled sensitivity and specificity of [18F]-labeled tracers were 0.82 (95% CI: 0.80-0.83) and 0.91 (95% CI: 0.90-0.92) when equivocal lesions were regarded as positive and 0.81 (95% CI: 0.80-0.82) and 0.91 (95% CI: 0.90-0.92) when equivocal lesions were considered to be negative. CONCLUSION: [18F]-labeled tracers have high diagnostic efficacy for lymph node/bone metastasis and biochemical recurrence in advanced PCa.

Diagnostic performance of CMR, SPECT, and PET imaging for the detection of cardiac amyloidosis: a meta-analysis.

BACKGROUND: Noninvasive myocardial imaging modalities, such as cardiac magnetic resonance (CMR), single photon emission computed tomography (SPECT), and Positron emission tomography (PET), are well-established and extensively used to detect cardiac amyloid (CA). The purpose of this study is to directly compare CMR, SPECT, and PET scans in the diagnosis of CA, and to provide evidence for further scientific research and clinical decision-making. METHODS: PubMed, Embase, and Cochrane Library were searched. Studies used CMR, SPECT and/or PET for the diagnosis of CA were included. Pooled sensitivity, specificity, positive and negative likelihood ratio (LR), diagnostic odds ratio (DOR), their respective 95% confidence intervals (CIs) and the area under the summary receiver operating characteristic (SROC) curve (AUC) were calculated. Quality assessment of included studies was conducted. RESULTS: A total of 31 articles were identified for inclusion in this meta-analysis. The pooled sensitivities of CMR, SPECT and PET were 0.84, 0.98 and 0.78, respectively. Their respective overall specificities were 0.87, 0.92 and 0.95. Subgroup analysis demonstrated that 99mTc-HMDP manifested the highest sensitivity (0.99). 99mTc-PYP had the highest specificity (0.95). The AUC values of 99mTc-DPD, 99mTc-PYP, 99mTc-HMDP were 0.89, 0.99, and 0.99, respectively. PET scan with 11C-PIB demonstrated a pooled sensitivity of 0.91 and specificity of 0.97 with an AUC value of 0.98. CONCLUSION: Our meta-analysis reveals that SEPCT scans present better diagnostic performance for the identification of CA as compared with other two modalities.

A pilot study of radiomics signature based on biparametric MRI for preoperative prediction of extrathyroidal extension in papillary thyroid carcinoma.

OBJECTIVE: To investigate efficiency of radiomics signature to preoperatively predict histological features of aggressive extrathyroidal extension (ETE) in papillary thyroid carcinoma (PTC) with biparametric magnetic resonance imaging findings. MATERIALS AND METHODS: Sixty PTC patients with preoperative MR including T2WI and T2WI-fat-suppression (T2WI-FS) were retrospectively analyzed. Among them, 35 had ETE and 25 did not. Pre-contrast T2WI and T2WI-FS images depicting the largest section of tumor were selected. Tumor regions were manually segmented using ITK-SNAP software and 107 radiomics features were computed from the segmented regions using the open Pyradiomics package. Then, a random forest model was built to do classification in which the datasets were partitioned randomly 10 times to do training and testing with ratio of 1:1. Furthermore, forward greedy feature selection based on feature importance was adopted to reduce model overfitting. Classification accuracy was estimated on the test set using area under ROC curve (AUC). RESULTS: The model using T2WI-FS image features yields much higher performance than the model using T2WI features (AUC = 0.906 vs. 0.760 using 107 features). Among the top 10 important features of T2WI and T2WI-FS, there are 5 common features. After feature selection, the models trained using top 2 features of T2WI and the top 6 features of T2WI-FS achieve AUC 0.845 and 0.928, respectively. Combining features computed from T2WI and T2WI-FS, model performance decreases slightly (AUC = 0.882 based on all features and AUC = 0.913 based on top features after feature selection). Adjusting hyper parameters of the random forest model have negligible influence on the model performance with mean AUC = 0.907 for T2WI-FS images. CONCLUSIONS: Radiomics features based on pre-contrast T2WI and T2WI-FS is helpful to predict aggressive ETE in PTC. Particularly, the model trained using the optimally selected T2WI-FS image features yields the best classification performance. The most important features relate to lesion size and the texture heterogeneity of the tumor region.

Preoperative assessment of extrathyroidal extension of papillary thyroid carcinomas by ultrasound and magnetic resonance imaging: a comparative study.

PURPOSE: The purpose of this study was to assess and compare the diagnostic performances of preoperative ultrasonography (US) and magnetic resonance imaging (MRI) in predicting extrathyroidal extension (ETE) in patients with papillary thyroid carcinoma (PTC). MATERIALS AND METHODS: This retrospective study was approved by our institutional review board. Preoperative US and MRI were performed on 225 patients who underwent surgery for PTC between May 2014 and December 2018. The US and MRI features of ETE of each case were retrospectively and independently investigated by two radiologists. The diagnostic performances of US and MRI, including their sensitivity, specificity, positive predictive values (PPV), and negative predictive values (NPV) for ETE, and their accuracy in predicting ETE were analyzed. RESULTS: Higher sensitivity and NPV in predicting minimal ETE were observed in US (87.5% and 76.2%, respectively) compared with MRI (71.3% and 61.7%, respectively) (p = 0.006 and p = 0.046, respectively). Meanwhile, MRI (85.4%) showed higher sensitivity than US (66.7%) in assessing extensive ETE (p = 0.005). MRI also showed significantly higher specificity and PPV than US in assessing overall ETE (p = 0.025 and p = 0.025, respectively). CONCLUSION: Preoperative US should be used as the first line in predicting minimal ETE, and MRI should be added in extensive ETE assessment. Compared with US, MRI had higher specificity and PPV in detecting the overall ETE of PTC.

Non-invasive glucagon-like peptide-1 receptor imaging in pancreas with (18)F-Al labeled Cys(39)-exendin-4.

PURPOSE: Glucagon-like peptide-1 receptor (GLP-1R) is abundantly expressed on beta cells and may be an ideal target for the pancreas imaging. Monitoring the GLP-1R of pancreas could be benefit for understanding the pathophysiology of diabetes. In the present study, (18)F-Al labeled exendin-4 analog, (18)F-Al-NOTA-MAL-Cys(39)-exendin-4, was evaluated for PET imaging GLP-1R in the pancreas. METHODS: The targeting of (18)F-Al labeled exendin-4 analog was examined in healthy and streptozotocin induced diabetic rats. Rats were injected with (18)F-Al-NOTA-MAL-Cys(39)-exendin-4 and microPET imaging was performed at 1 h postinjection, followed by ex vivo biodistribution. GLP-1R expression in pancreas was determined through post mortern examinations. RESULTS: The pancreas of healthy rats was readily visualized after administration of (18)F-Al-NOTA-MAL-Cys(39)-exendin-4, whereas the pancreas of diabetic rats, as well as those from rats co-injected with excess of unlabeled peptides, was barely visible by microPET. At 60 min postinjection, the pancreatic uptakes were 1.02 ± 0.15%ID/g and 0.23 ± 0.05%ID/g in healthy and diabetic rats respectively. Under block, the pancreatic uptakes of non-diabetic rats reduced to 0.21 ± 0.07%ID/g at the same time point. Biodistribution data and IHC staining confirmed the findings of the microPET imaging. CONCLUSION: The favorable preclinical data indicated that (18)F-Al-NOTA-MAL-Cys(39)-exendin-4may be suitable for non-invasive monitoring functional pancreatic beta cells.

(18)F-Alfatide II PET/CT in healthy human volunteers and patients with brain metastases.

PURPOSE: We report the biodistribution and radiation dosimetry of an integrin αvß3 specific PET tracer (18)F-AlF-NOTA-E[PEG4-c(RGDfk)]2) (denoted as (18)F-Alfatide II). We also assessed the value of (18)F-Alfatide II in patients with brain metastases. METHODS: A series of torso (from the skull to the thigh) static images were acquired in five healthy volunteers (3 M, 2 F) at 5, 10, 15, 30, 45, and 60 min after injection of (18)F-Alfatide II (257 ± 48 MBq). Regions of interest (ROIs) were drawn manually, and the time-activity curves (TACs) were obtained for major organs. Nine patients with brain metastases were examined by static PET imaging with (18)F-FDG (5.55 MBq/kg) and (18)F-Alfatide II. RESULTS: Injection of (18)F-Alfatide II was well tolerated in all healthy volunteers, with no serious tracer-related adverse events found. (18)F-Alfatide II showed rapid clearance from the blood pool and kidneys. The total effective dose equivalent (EDE) and effective dose (ED) were 0.0277 ± 0.003 mSv/MBq and 0.0198 ± 0.002 mSv/MBq, respectively. The organs with the highest absorbed dose were the kidneys and the spleen. Nine patients with 20 brain metastatic lesions identified by MRI and/or CT were enrolled in this study. All 20 brain lesions were visualized by (18)F-Alfatide II PET, while only ten lesions were visualized by (18)F-FDG, and 13 by CT. CONCLUSION: F-Alfatide II is a safe PET tracer with a favorable dosimetry profile. The observed ED suggests that (18)F-Alfatide II is feasible for human studies. (18)F-Alfatide II has potential value in finding brain metastases of different cancers as a biomarker of angiogenesis.

Research progress on asialoglycoprotein receptor-targeted radiotracers designed for hepatic nuclear medicine imaging.

Asialoglycoprotein receptor (ASGPR) specifically recognizes glycans terminated with ß-d-galactose or N-acetylgalactosamine. Its exclusive expression in mammalian hepatocytes renders it an ideal hepatic-targeted biomarker. To date, ASGPR-targeted ligands have been actively developed for drug delivery and hepatic imaging. This review provides a comprehensive summary of the progress achieved to-date in the field of developing ASGPR-targeted nuclear medicine imaging (NMI) radiotracers, highlighting the recent advancements over the last decade in terms of structure, radionuclides and labeling strategies. The biodistribution patterns, imaging characteristics, challenges and future prospective are discussed.

Imaging diagnosis and efficacy monitoring by [89Zr]Zr-DFO-KN035 immunoPET in patients with PD-L1-positive solid malignancies.

Rationale: Although programmed death-ligand 1 (PD-L1) inhibitors have achieved efficacy in cancer therapy, their response rate is low. Differences in the prognosis of patients with cancer under anti-PD-L1 treatment are related to the PD-L1 level in tumors. Accurate PD-L1 detection can optimize the accuracy of tumor immunotherapy and avoid ineffective clinical diagnosis and treatments. Methods: We investigated the imaging efficiency and therapy monitoring capacity of [89Zr]Zr-DFO-KN035 immunoPET for tumors. We labeled the monodomain anti-PD-L1 antibody KN035 with the radionuclide zirconium-89 and used this tracer for PET imaging. [89Zr]Zr-DFO-KN035 uptakes in patients with PD-L1-positive tumors, including primary and metastatic tumors, as well as in normal tissues, were comparatively assessed by using positron emission tomography/computed tomography imaging. Results: In PD-L1-positive patients, [89Zr]Zr-DFO-KN035 was sensitive in tumor-targeting imaging and could detect multiple metastatic foci, including multiple bone metastases (tumor-to-muscle ratios of 7.102 and 6.118 at 55 and 120 h, respectively) and lymph-node metastases (tumor-to-muscle ratios of 11.346 and 6.542 at 55 and 120 h, respectively). The needed radioactive dose of [89Zr]Zr-DFO-KN035 (55.5-92.5 MBq) used in this study was considerably lower than that of [18F]FDG (370-555 MBq). [89Zr]Zr-DFO-KN035 monitored and predicted the site of adverse reactions in antitumor immunotherapy. Moreover, after antitumor treatment, [89Zr]Zr-DFO-KN035 enabled observational imaging for therapeutic efficacy evaluation, which can help predict patient prognosis. Conclusion: [89Zr]Zr-DFO-KN035 can be used for the diagnosis and therapy monitoring of PD-L1-positive tumors and provide noninvasive and comprehensive observations for tumor diagnostic imaging, prognosis prediction, and efficacy evaluation.

A pan-KRAS degrader for the treatment of KRAS-mutant cancers.

KRAS mutations are highly prevalent in a wide range of lethal cancers, and these mutant forms of KRAS play a crucial role in driving cancer progression and conferring resistance to treatment. While there have been advancements in the development of small molecules to target specific KRAS mutants, the presence of undruggable mutants and the emergence of secondary mutations continue to pose challenges in the clinical treatment of KRAS-mutant cancers. In this study, we developed a novel molecular tool called tumor-targeting KRAS degrader (TKD) that effectively targets a wide range of KRAS mutants. TKD is composed of a KRAS-binding nanobody, a cell-penetrating peptide selectively targeting cancer cells, and a lysosome-binding motif. Our data revealed that TKD selectively binds to KRAS in cancer cells and effectively induces KRAS degradation via a lysosome-dependent process. Functionally, TKD suppresses tumor growth with no obvious side effects and enhances the antitumor effects of PD-1 antibody and cetuximab. This study not only provides a strategy for developing drugs targeting "undruggable" proteins but also reveals that TKD is a promising therapeutic for treating KRAS-mutant cancers.

Advances in superparamagnetic iron oxide nanoparticles modified with branched polyethyleneimine for multimodal imaging.

Multimodal imaging are approaches which combines multiple imaging techniques to obtain multi-aspect information of a target through different imaging modalities, thereby greatly improve the accuracy and comprehensiveness of imaging. Superparamagnetic iron oxide nanoparticles (SPIONs) modified with branched polyethyleneimine have revealed good biocompatibility and stability, high drug loading capacity and nucleic acid transfection efficiency. SPIONs have been developed as functionalized platforms which can be further modified to enhance their functionalities. Those further modifications facilitate the application of SPIONs in multimodal imaging. In this review, we discuss the methods, advantages, applications, and prospects of BPEI-modified SPIONs in multimodal imaging.

Metabolite-assisted models improve risk prediction of coronary heart disease in patients with diabetes.

Background: Patients with diabetes have a two-to four-fold increased incidence of cardiovascular diseases compared with non-diabetics. Currently, there is no recognized model to predict the occurrence and progression of CVDs in diabetics. Objective: This work aimed to develop a metabolic biomarker-assisted model, a combination of metabolic markers with clinical variables, for risk prediction of CVDs in diabetics. Methods: A total of 475 patients with diabetes were studied. Each patient underwent coronary angiography. Plasma samples were analyzed by liquid chromatography-quadrupole time-of-flight mass spectrometry. Ordinal logistic regression and random forest were used to screen metabolites. Receiver operating characteristic (ROC) curve, nomogram, and decision curve analysis (DCA) were employed to evaluate their prediction performances. Results: Ordinal logistic regression screened out 34 differential metabolites (adjusted-false discovery rate p < 0.05) from 2059 ion features by comparisons of diabetics with and without CVDs. Random forest identified methylglutarylcarnitine and lysoPC (18:0) as the metabolic markers (mean decrease gini >1.0) for non-significant CVDs (nos-CVDs) versus normal coronary artery (NCA), 1,3-Octadiene and 3-Octanone for acute coronary syndrome (ACS) versus nos-CVDs, and lysoPC (18:0) for acute coronary syndrome versus normal coronary artery. For risk prediction, the metabolic marker-assisted models provided areas under the curve of 0.962-0.979 by ROC (0.576-0.779 for the base models), and c-indices of 0.8477-0.9537 by nomogram analysis (0.1514-0.5196 for the base models). Decision curve analysis (DCA) showed that the models produced greater benefits throughout a wide range of risk probabilities compared with the base model. Conclusion: Metabolic biomarker-assisted model remarkably improved risk prediction of cardiovascular disease in diabetics (>90%).

Bibliometric analysis of ferroptosis: a comprehensive evaluation of its contribution to cancer immunity and immunotherapy.

Background: In the past 5 years, ferroptosis-associated cancer immunity has been attracted significant research interest. Objective: This study was performed to identify and analyze the global output trend for ferroptosis in cancer immunity. Methods: Relevant studies were retrieved from the Web of Science Core Collection on Feb 10th, 2023. The VOSviewer and Histcite softwares were utilized to perform the visual bibliometric and deep mining analyses. Results: A total of 694 studies (530 articles (76.4%) and 164 (23.6%) review articles) were retrieved from the Web of Science Core Collection for visualization analyses. The top 3 key keywords were ferroptosis, prognosis and immunotherapy. The top 30 local citation score (LCS) authors were all collaborators of Zou Weiping. Deep mining of 51 nanoparticle-related articles showed that BIOMATERIALS was the most popular journal. The primary goal of gene signatures related to ferroptosis and cancer immunity was to establish prognostic predictions. Conclusion: There has been a significant increase in ferroptosis-associated immune publications in the recent 3 years. The key research hotspots include mechanisms, prediction and therapeutic outcomes. The most influential article was from the Zou Weiping's group, which proposed that system xc-mediated ferroptosis is induced by CD8(+) T cell-secreted IFNγ after PD-L1 blockage for immunotherapy. The frontier of research in the field of ferroptosis-associated immune is the study on nanoparticle and gene signature The limitation of this bibliometric study is that publications on this topic are few.