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Lymphoma is a heterogeneous disease with varying clinical manifestations and outcomes. Many subtypes of lymphoma, such as Burkitt′s lymphoma and diffuse large B cell lymphoma, are highly aggressive with dismal prognosis even after conventional chemotherapy and radiotherapy. As such, exploring specific biomarkers for lymphoma is of high clinical significance. Herein, a potential marker, CD38, is investigated for differentiating lymphoma. A CD38‐targeting monoclonal antibody (mAb, daratumumab) is then radiolabeled with Zr‐89 and Lu‐177 for theranostic applications. As the diagnostic component, the Zr‐89‐labeled mAb is highly specific in delineating CD38‐positive lymphoma via positron emission tomography (PET) imaging, while the Lu‐177‐labeled mAb serves well as the therapeutic component to suppress tumor growth after a one‐time administration. These results strongly suggest that CD38 is a lymphoma‐specific marker and prove that 89Zr/177Lu‐labeled daratumumab facilitates immunoPET imaging and radioimmunotherapy of lymphoma in preclinical models. Further clinical evaluation and translation of this CD38‐targeted theranostics may be of significant help in lymphoma patient stratification and management. [ABSTRACT FROM AUTHOR]

Hydrogen sulfide (H2S) is of vital importance in several biological and physical processes. The significance of H2S‐specific detection and monitoring is emphasized by its elevated levels in various diseases such as cancer. Nanotechnology enhances the performance of chemical sensing nanoprobes due to the enhanced efficiency and sensitivity. Recently, extensive research efforts have been dedicated to developing novel smart H2S‐triggered/therapeutic system (SHTS) nanoplatforms for H2S‐activated sensing, imaging, and therapy. Herein, the latest SHTS‐based nanomaterials are summarized and discussed in detail. In addition, therapeutic strategies mediated by endogenous H2S as a trigger or exogenous H2S delivery are also included. A comprehensive understanding of the current status of SHTS‐based strategies will greatly facilitate innovation in this field. Lastly, the challenges and key issues related to the design and development of SHTS‐based nanomaterials (e.g., morphology, surface modification, therapeutic strategies, appropriate application, and selection of nanomaterials) are outlined. [ABSTRACT FROM AUTHOR]

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease resulting in irreversible scarring within the lungs. However, the lack of biomarkers that enable real-time assessment of disease activity remains a challenge in providing efficient clinical decision-making and optimal patient care in IPF. Fibronectin (FN) is highly expressed in fibroblastic foci of the IPF lung where active extracellular matrix (ECM) deposition occurs. Functional upstream domain (FUD) tightly binds the N-terminal 70-kilodalton domain of FN that is crucial for FN assembly. In this study, we first demonstrate the capacity of PEGylated FUD (PEG-FUD) to target FN deposition in human IPF tissue ex vivo. We subsequently radiolabeled PEG-FUD with 64Cu and monitored its spatiotemporal biodistribution via µPET/CT imaging in mice using the bleomycin-induced model of pulmonary injury and fibrosis. We demonstrated [64Cu] Cu-PEG-FUD uptake 3 and 11 days following bleomycin treatment, suggesting that radiolabeled PEG-FUD holds promise as an imaging probe in aiding the assessment of fibrotic lung disease activity. [ABSTRACT FROM AUTHOR]

CD20-overexpressed non-Hodgkin lymphoma typically indicates progressive malignancy. Obinutuzumab is a next-generation Food and Drug Administration-approved humanized monoclonal antibody that targets CD20. Previous studies with 89 Zr-labeled obinutuzumab have successfully imaged CD20 in vivo. However, delayed tumor uptake and increased radioactive exposure caused by long blood circulation limit its clinical translation. This study aimed to develop 64 Cu-labeled F(ab') 2 fragments of obinutuzumab for imaging CD20 in lymphoma xenograft tumor models. Methods: F(ab') 2 fragments were produced from obinutuzumab using an IgG-degrading enzyme of Streptococcus pyogenes (IdeS) enzyme and purified with protein A beads. Sodium dodecyl sulfate polyacrylamide gel electrophoresis and high-performance liquid chromatography were performed to evaluate the products and their stability. F(ab') 2 products were conjugated with p-SCN-Bn-NOTA (NOTA) for 64 Cu radiolabeling. Western blotting was performed to screen the CD20 expression levels of lymphoma cells. Enzyme-linked immunosorbent assay, flow cytometry, and confocal imaging were used to test the binding affinity in vitro. Serial PET imaging and biodistribution studies in subcutaneous lymphoma-bearing mice were performed using 64 Cu-NOTA-F(ab') 2 -obinutuzumab or 64 Cu-NOTA-F(ab') 2 -IgG. Results: F(ab') 2 -obinutuzumab and F(ab') 2 -IgG produced by the IdeS digestion system were confirmed with sodium dodecyl sulfate polyacrylamide gel electrophoresis and high-performance liquid chromatography. The radiochemical purity of 64 Cu-labeled F(ab') 2 fragments was no less than 98%, and the specific activity was 56.3 ± 7.9 MBq/mg ( n = 6). Among the 5 lymphoma cell lines, Ramos showed the strongest expression of CD20, and CLL-155 showed the lowest, as confirmed by enzyme-linked immunosorbent assay, flow cytometry, and confocal imaging. PET imaging revealed rapid and sustained tumor uptake of 64 Cu-NOTA-F(ab') 2 -obinutuzumab in Ramos tumor-bearing mice. The peak tumor uptake (9.08 ± 1.67 percentage injected dose per gram of tissue [%ID/g]) in the Ramos model was significantly higher than that in the CCL-155 model (2.78 ± 0.62 %ID/g) or the 64 Cu-NOTA-F(ab') 2 -IgG control (1.93 ± 0.26 %ID/g, n = 4, P < 0.001). The tumor-to-blood and tumor-to-muscle ratios were 7.3 ± 1.6 and 21.9 ± 9.0, respectively, at 48 h after injection in the 64 Cu-NOTA-F(ab') 2 -obinutuzumab group. Of the measured off-target organs, the kidneys showed the highest uptake. Ex vivo immunofluorescent staining verified the differential CD20 expression in the Ramos and CCL-155 tumor models. Conclusion: This study demonstrated that 64 Cu-NOTA-F(ab') 2 -obinutuzumab had a rapid and sustained tumor uptake in CD20-positive lymphoma with high contrast, which could enable noninvasive evaluation of CD20 levels in the clinic., (© 2021 by the Society of Nuclear Medicine and Molecular Imaging.)