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Purpose: Abnormal CD38 expression in some hematologic malignancies, including lymphoma, has made it a biomarker for targeted therapies. Daratumumab (Dara) is the first FDA-approved CD38-specific monoclonal antibody, enabling successfully immunoPET imaging over the past years. Radiolabeled Dara however has a long blood circulation and delayed tumor uptake which can limit its applications. The focus of this study is to develop 64Cu-labeled Dara-F(ab′)2 for the visualization of CD38 in lymphoma models. Methods: F(ab′)2 fragment was prepared from Dara using an IdeS enzyme and purified with Protein A beads. Western blotting, flow cytometry, and surface plasmon resonance (SPR) were performed for in vitro assay. Probes were labeled with 64Cu after the chelation of 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA). Small animal PET imaging and quantitative analysis were performed after injection of 64Cu-labeled Dara-F(ab′)2, IgG-F(ab′)2, and Dara for evaluation in lymphoma models. Results: Flow cytometry and SPR assay proved the specific binding ability of Dara-F(ab′)2 and NOTA-Dara-F(ab′)2 in vitro. Radiolabeling yield of [64Cu]Cu-NOTA-Dara-F(ab′)2 was over 90% and with a specific activity of 4.0 ± 0.6 × 103 MBq/μmol (n = 5). PET imaging showed [64Cu]Cu-NOTA-Dara-F(ab′)2 had a rapid and high tumor uptake as early as 2 h (6.9 ± 1.2%ID/g) and peaked (9.5 ± 0.7%ID/g) at 12 h, whereas [64Cu]Cu-NOTA-Dara reached its tumor uptake peaked at 48 h (8.3 ± 1.4%ID/g, n = 4). In comparison, IgG-F(ab′)2 and HBL-1 control groups found no noticeable tumor uptake. [64Cu]Cu-NOTA-Dara-F(ab′)2 had significantly lower uptake in blood pool, bone, and muscle than [64Cu]Cu-NOTA-Dara and its tumor-to-blood and tumor-to-muscle ratios were significantly higher than controls. Conclusions: [64Cu]Cu-NOTA-Dara-F(ab′)2 showed a rapid and high tumor uptake in CD38-positive lymphoma models with favorable imaging contrast, showing its promise as a potential PET imaging agent for future clinical applications. [ABSTRACT FROM AUTHOR]

Although the development of energy and mineral resources strongly supports China's rapid industrialization and urbanization, it has led to a series of ecological and environmental problems. Strengthening the spatial regulation considering the ecological and environmental protection on energy and mineral resource development areas is an important aspect of realizing China's sustainable development. In this study, we mapped, categorized, and analyzed the ecological cumulative effects of the Chinese 134 prefectural mining units based on the pressure-state-response model, which is demonstrated as impact of mining activities on ecological environment, ecological environmental fragility, and ecological function. This investigation developed a stress zoning typology of the mining units based on scores of three dimensions of the ecological cumulative effects and classified 134 prefectural mining units into eight types of stress zones. A series of regulation and policy suggestions have been proposed to different types of zones from three aspects: space control, intensity control, and development mode control. The application of this evaluation and spatial zoning system will contribute to the refined spatial management of China's mining areas. [ABSTRACT FROM AUTHOR]

Highlights: The vertically aligned structures of anisotropic fillers (using 2D boron nitride (BN) platelets as a proof-of-concept) in composites are constructed assisted by the expansion flow. BN platelets in composites are aligned in a curved shape that includes vertical alignment in the central area and horizontal alignment close to strip surfaces. The shape of expansion channels affects the vertical orientation order and the through-plane thermal conductivity of composites.Orientation control of anisotropic one-dimensional (1D) and two-dimensional (2D) materials in solutions is of great importance in many fields ranging from structural materials design, the thermal management, to energy storage. Achieving fine control of vertical alignment of anisotropic fillers (such as graphene, boron nitride (BN), and carbon fiber) remains challenging. This work presents a universal and scalable method for constructing vertically aligned structures of anisotropic fillers in composites assisted by the expansion flow (using 2D BN platelets as a proof-of-concept). BN platelets in the silicone gel strip are oriented in a curved shape that includes vertical alignment in the central area and horizontal alignment close to strip surfaces. Due to the vertical orientation of BN in the central area of strips, a through-plane thermal conductivity as high as 5.65 W m−1 K−1 was obtained, which can be further improved to 6.54 W m−1 K−1 by combining BN and pitch-based carbon fibers. The expansion-flow-assisted alignment can be extended to the manufacture of a variety of polymer composites filled with 1D and 2D materials, which can find wide applications in batteries, electronics, and energy storage devices. [ABSTRACT FROM AUTHOR]

A recent article in the European Journal of Nuclear Medicine & Molecular Imaging discusses the development of a macrocyclic peptide PET radioligand for PD-L1, a protein involved in immune checkpoint mechanisms. The article highlights the challenges and opportunities in individualizing treatment for patients who could benefit from anti-PD-1/PD-L1 therapy and monitoring their response during therapy. The authors present a study on the discovery and evaluation of a novel fluorine-18 labeled macrocyclic peptide-based PET ligand, [18F]BMS-986229, which demonstrated high affinity for PD-L1 and rapid clearance from non-PD-L1 tissues. The study suggests that this ligand has the potential to facilitate a broader clinical application of PD-L1 PET imaging. [Extracted from the article]

This article discusses the use of radiomics, a method that involves extracting imaging features from radiologic images, to predict lymph node metastasis (LNM) in colorectal cancer (CRC) patients. The study found that radiomics analysis using 2-[18F]FDG PET-based imaging was more effective in predicting LNM compared to traditional CT and PET reports. The study also highlighted the need for standardization in radiomics workflow and the development of automated segmentation tools. While promising, further research and validation in larger clinical trials are needed before radiomics can be integrated into routine clinical practice. [Extracted from the article]

Purpose: Triple-negative breast cancer (TNBC) has a poor prognosis due to the absence of effective therapeutic targets. Vascular endothelial growth factor (VEGF) family are expressed in 30–60% of TNBC, therefore providing potential therapeutic targets for TNBC. Aflibercept (Abe), a humanized recombinant fusion protein specifically bound to VEGF-A, B and placental growth factor (PIGF), has proven to be effective in the treatment in some cancers. Therefore, 89Zr/177Lu-labeled Abe was investigated for its theranostic role in TNBC. Methods: Abe was radiolabeled with 89Zr and 177Lu via the conjugation of chelators. Flow cytometry and cell immunofluorescent staining were performed to evaluate the binding affinity of Abe. Sequential PET imaging and fluorescent imaging were conducted in TNBC tumor bearing mice following the injection of 89Zr-labeled Abe and Cy5.5-labeled Abe. Treatment study was performed after the administration of 177Lu-labeled Abe. Tumor volume and survival were monitored and SPECT imaging and biodistribution studies were conducted. Safety evaluation was performed including body weight, blood cell measurement, and hematoxylin–eosin (H&E) staining of major organs. Expression of VEGF and CD31 was tested by immunohistochemical staining. Dosimetry was estimated using the OLINDA software. Results: FITC-labeled Abe showed a strong binding affinity to VEGF in TNBC 4T1 cells and HUVECs by flow cytometry and cell immunofluorescence. Tumor uptake of 89Zr-labeled Abe peaked at 120 h (SUVmax = 3.2 ± 0.64) and persisted before 168 h (SUVmax = 2.54 ± 0.42). The fluorescence intensity of the Cy5.5-labeled Abe group surpassed that of the Cy5.5-labeled IgG group, implying that Cy5.5-labeled Abe is a viable candidate monitoring in vivo tumor targeting and localization. 177Lu-labeled Abe (11.1 MBq) served well as the therapeutic component to suppress tumor growth with standardized tumor volume at 16 days, significantly smaller than PBS group (about 815.66 ± 3.58% vs 3646.52 ± 11.10%, n = 5, P < 0.01). Moreover, SPECT images confirmed high contrast between tumors and normal organs, indicating selective tumor uptake of 177Lu-labeled Abe. No discernible abnormalities in blood cells, and no evident histopathological abnormality observed in liver, spleen, and kidney. Immunohistochemical staining showed that 177Lu-labeled Abe effectively inhibited the expression of VEGF and CD31 of tumor, suggesting that angiogenesis may be suppressed by 177Lu-labeled Abe. The whole-body effective dose for an adult human was estimated to be 0.16 mSv/MBq. Conclusion: 89Zr/177Lu-labeled Abe could be a TNBC-specific marker with diagnostic value and provide insights into targeted therapy in the treatment of TNBC. Further clinical evaluation and translation may be of high significance for TNBC. [ABSTRACT FROM AUTHOR]

Background: Chylothorax is a condition that can be challenging to diagnose due to its nonspecific clinical presentation. Several biochemical parameters of chylous pleural effusion have been identified as important indicators for the diagnosis of chylothorax. Lymphoscintigraphy is utilized to assess chylothorax and determine the location of chyle leakage. The present study aimed to evaluate the correlation between the biochemical parameters of chylous pleural effusion and 99mTc-dextran (99mTc-DX) lymphoscintigraphy in diagnosing chylothorax. Material and methods: A total of 120 patients were enrolled in the study, 83 of the patients with unilateral chylothorax, and 37 with bilateral chylothorax. All patients underwent both 99mTc-DX lymphoscintigraphy and pleural effusion laboratory analysis. The 99mTc-DX lymphoscintigraphy images were categorized as positive or negative groups based on the presence or absence of abnormal radioactive tracer accumulation in the thorax, respectively. The biochemical parameters of the two groups were subsequently compared. Results: Among these patients, 101 (84.17%) had exudative effusions, while 19 (15.83%) had transudative effusions, as determined by the levels of pleural effusion protein, lactate dehydrogenase and cholesterol. Abnormal tracer accumulation in thorax was observed in 82 patients (68.33%). Our findings indicated that lymphoscintigraphy results were not associated with exudative and transudative chylothorax (P = 0.597). The lymphoscintigraphy positive group displayed significantly higher levels of pleural effusion triglyceride and pleural effusion triglyceride/serum triglyceride ratio in all biochemical parameters, compared to the negative group (P = 0.000 and P = 0.005). We identified cutoff values of 2.870 mmol/L for pleural effusion triglycerides and 4.625 for pleural effusion triglyceride/serum triglyceride ratio, respectively, which can facilitate differentiating the positive and negative cases on lymphoscintigraphy. Conclusion: Lymphoscintigraphy technique is a dependable diagnostic tool for the qualitative assessment of chylous pleural effusion. Higher pleural effusion triglyceride level and pleural effusion triglyceride/serum triglyceride ratio indicate a positive result in patients with chylothorax on lymphoscintigraphy, with the cutoff values of 2.870 mmol/L and 4.625 aiding in the diagnosis. [ABSTRACT FROM AUTHOR]

Purpose: Pancreatic cancer is a malignant tumor with a high degree of malignancy, strong heterogeneity, and high lethality. Trop2 is a transmembrane glycoprotein associated with the occurrence, development, and poor prognosis of pancreatic cancer. This study aims to develop 64Cu/177Lu-labeled anti-Trop2 monoclonal antibody (hIMB1636) for positron emission tomography (PET) imaging and radioimmunotherapy (RIT) application in pancreatic cancer tumor models. Methods: The binding kinetics of hIMB1636 to Trop2 antigen was measured by Biolayer interferometry (BLI). Western blotting was used to screen the Trop2 expression of pancreatic cancer cell lines. Flow cytometry and cell immunofluorescence were used to evaluate the binding ability of hIMB1636 and Trop2 on the cell surface. hIMB1636 were conjugated with p-SCN-Bn-NOTA (NOTA) and DOTA-NHS-ester (DOTA) for 64Cu and 177Lu radiolabeling respectively. ImmunoPET imaging and RIT studies were performed using 64Cu-NOTA-hIMB1636 and 177Lu-DOTA-hIMB1636 in subcutaneous pancreatic cancer tumor models. Results: hIMB1636 had a strong binding affinity to Trop2 according to the results of BLI. The T3M-4 cell line showed the strongest expression of Trop2 and specific binding ability of hIMB1636 according to the results of Western blotting, flow cytometry, and cell immunofluorescence. The radiochemical purity of 64Cu-NOTA-hIMB1636 and 177Lu-DOTA-hIMB1636 exceeded 95%. PET imaging showed gradually an accumulation of 64Cu-NOTA-hIMB1636 in T3M-4 tumor models. The maximum tumor uptake was 8.95 ± 1.07%ID/g (n = 4) at 48 h post injection (p.i.), which had significant differences with T3M-4-blocked and PaTu8988-negative groups (P < 0.001). The high-177Lu-hIMB1636 group demonstrated the strongest tumor suppression with standardized tumor volume about 94.24 ± 14.62% (n = 5) at 14 days p.i., significantly smaller than other groups (P < 0.05). Ex vivo biodistribution and histological staining verified the in vivo PET imaging and RIT results. Conclusions: This study demonstrated that 64Cu/177Lu-labeled hIMB1636 could noninvasively evaluate the expression level of Trop2 and inhibit the Trop2-overexpressed tumor growth in pancreatic cancer tumor models. Further clinical evaluation and translation of Trop2-targeted drug may be of great help in the stratification and management of pancreatic cancer patients. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "Theranostic role of 89Zr- and 177Lu-labeled aflibercept in breast cancer" published in the European Journal of Nuclear Medicine & Molecular Imaging. The correction states that the order of the names in the corresponding authors' details section was interchanged, and Dr. Kang should be listed before Dr. Li. The original article has been corrected. The publisher, Springer Nature, remains neutral regarding jurisdictional claims and institutional affiliations. The authors of the article are Qi Yang, Zhao Chen, Yongkang Qiu, Wenpeng Huang, Tianyao Wang, Lele Song, Xinyao Sun, Cuicui Li, Xiaojie Xu, and Lei Kang. [Extracted from the article]