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  • American Association for Cancer Research (AACR)  (2)
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  • American Association for Cancer Research (AACR)  (2)
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  • 1
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 26, No. 9 ( 2020-05-01), p. 2140-2150
    Abstract: Human B7-H3 (hB7-H3) is a promising molecular imaging target differentially expressed on the neovasculature of breast cancer and has been validated for preclinical ultrasound (US) imaging with anti–B7-H3-antibody-functionalized microbubbles (MB). However, smaller ligands such as affibodies (ABY) are more suitable for the design of clinical-grade targeted MB. Experimental Design: Binding of ABYB7-H3 was confirmed with soluble and cell-surface B7-H3 by flow cytometry. MB were functionalized with ABYB7-H3 or anti–B7-H3-antibody (AbB7-H3). Control and targeted MB were tested for binding to hB7-H3–expressing cells (MS1hB7-H3) under shear stress conditions. US imaging was performed with MBABY-B7-H3 in an orthotopic mouse model of human MDA-MB-231 coimplanted with MS1hB7-H3 or control MS1WT cells and a transgenic mouse model of breast cancer development. Results: ABYB7-H3 specifically binds to MS1hB7-H3 and murine-B7-H3–expressing monocytes. MBABY-B7-H3 (8.5 ± 1.4 MB/cell) and MBAb-B7-H3 (9.8 ± 1.3 MB/cell) showed significantly higher (P & lt; 0.0001) binding to the MS1hB7-H3 cells compared with control MBNon-targeted (0.5 ± 0.1 MB/cell) under shear stress conditions. In vivo, MBABY-B7-H3 produced significantly higher (P & lt; 0.04) imaging signal in orthotopic tumors coengrafted with MS1hB7-H3 (8.4 ± 3.3 a.u.) compared with tumors with MS1WT cells (1.4 ± 1.0 a.u.). In the transgenic mouse tumors, MBABY-B7-H3 (9.6 ± 2.0 a.u.) produced higher (P & lt; 0.0002) imaging signal compared with MBNon-targeted (1.3 ± 0.3 a.u.), whereas MBABY-B7-H3 signal in normal mammary glands and tumors with B7-H3 blocking significantly reduced (P & lt; 0.02) imaging signal. Conclusions: MBABY-B7-H3 enhances B7-H3 molecular signal in breast tumors, improving cancer detection, while offering the advantages of a small size ligand and easier production for clinical imaging.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2020
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    detail.hit.zdb_id: 2036787-9
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  • 2
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2023
    In:  Cancer Research Vol. 83, No. 8_Supplement ( 2023-04-14), p. LB115-LB115
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 83, No. 8_Supplement ( 2023-04-14), p. LB115-LB115
    Abstract: Ultrasound contrast agent (UCA) based molecular imaging is a rapidly growing field in biomedical research. Ultrasound (US) is a non-radiative imaging modality that is frequently used to investigate various human diseases in the clinic. US molecular imaging is a novel imaging modality that utilizes targeted contrast agents to add molecular information about the imaging target, including vascular biomarkers of cancer. Pre-clinical animal models are commonly used to evaluate and validate targeted contrast agents before extending them for FDA-approval. Key impediments in the preclinical evaluations are the short in vivo half-life of microbubbles (MBs) (less than 30 minutes), limited transducer scanning area, and focusing one target at a time, which all make this strategy low throughput. Moreover, whole-body imaging strategy is not available for US imaging compared to other imaging modalities, such as PET, CT, and MRI. To overcome these imitations, we have developed a multi-mouse US imaging platform using an Automated Breast Volume Scanner (ABVS) system. In addition, we have synthesized a novel breast cancer vascular-specific B7-H3 targeted microbubbles (TMBs) using a microfluidic device. We tested these TMBs in a genetically engineered transgenic mice model [FVB/N-Tg (MMTV-PyMT)634Mul/J] (n=32) that develops breast cancer in the mammary fat pad. The US imaging results of conventional Vevo 2100 system indicated that B7-H3-TMBs could provide target specific contrast signals in the tumor vasculature compared to control MBs. We used this MBs for whole-body imaging using an ABVS system with two mice simultaneously in a stage. We imaged multiple tumors (10 tumors/mouse, 2 mice per scan, n=20 tumors) with a single bolus injection of TMBs per mouse. The results successfully showed tumor specific contrast signals from tumors independent of tumor size. Introduction of this whole-body scanner, and its ability to scan multiple mice simultaneously allows rapid imaging of multiple tumors with 3D quantification of tumor size by administering a single TMB injection enabling without significant contrast loss. Our approach makes this US-MI as high throughput and can be used to test multiple contrast agents for investigating different aspects of biological problems including screening of vascular biomarkers of human diseases. Citation Format: Arutselvan Natarajan, Farbod Tabesh, Dongwoon Hyun, Ramasamy Paulmurugan, Jeremy Dahl. Simultaneous whole-body ultrasound contrast imaging: a novel high throughput preclinical platform for targeted molecular imaging studies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB115.
    Type of Medium: Online Resource
    ISSN: 1538-7445
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2023
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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