Evaluation of Antiatherogenic Properties of Ezetimibe Using 3H-Labeled Low-Density-Lipoprotein Cholesterol and 99mTc-cAbVCAM1–5 SPECT in ApoE−/− Mice Fed the Paigen Diet

Dumas, Laurent; Briand, François; Clerc, R.; Brousseau, Emmanuel; Montemagno, Christopher; Ahmadi, Mitra; Bacot, Sandrine; Soubies, Audrey; Perret, Pascale; Riou, Laurent; Devoogdt, Nick; Lahoutte, Tony; Barone-Rochette, Gilles; Fagret, Daniel; Ghezzi, Cathérine; Sulpice, Thierry; Broisat, Alexis

doi:10.2967/jnumed.116.177279

Cited by 20 publications

(10 citation statements)

References 19 publications

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“…Otherwise, the specificity of dual-MPIO could be further increased in the future by replacing the two separate antibodies that target VCAM-1 and P-selectin with bispecific antibodies that simultaneously target both VCAM-1 and P-selectin [87]. In vivo: ApoE −/− on WD; In vivo: effect of statins on the atherosclerotic lesions in ApoE −/− on WD; In vivo: effect of ezetimibe on the atherosclerotic lesions in ApoE -/on Paigen Diet [111][112][113] Nuclear imaging Fluorine-18 Nanobody (cAbVCAM-1-5)…”

Section: Imaging Of Vcam-1mentioning

confidence: 99%

“…Therefore, Broisat et al generated the technetium-99m-labeled anti-VCAM-1 nanobody ([ 99m Tc]Tc-cAbVCAM-1-5) recognising mouse and human homologues that successfully detect atherosclerosis by SPECT/CT imaging [111]. [ 99m Tc]Tc-cAbVCAM-1-5 was also used to demonstrate the antiatherogenic effect of statins [112] and ezetimibe [113] in a mouse model of atherosclerosis. It is a specific, sensitive and reproducible tool for the non-invasive imaging of atherosclerosis and the evaluation of novel antiatherogenic agents, which requires clinical validation.…”

Section: Imaging Of Vcam-1mentioning

confidence: 99%

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VCAM-1 Target in Non-Invasive Imaging for the Detection of Atherosclerotic Plaques

Thayse

Kindt

Laurent

et al. 2020

Biology

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Atherosclerosis is a progressive chronic arterial disease characterised by atheromatous plaque formation in the intima of the arterial wall. Several invasive and non-invasive imaging techniques have been developed to detect and characterise atherosclerosis in the vessel wall: anatomic/structural imaging, functional imaging and molecular imaging. In molecular imaging, vascular cell adhesion molecule-1 (VCAM-1) is a promising target for the non-invasive detection of atherosclerosis and for the assessment of novel antiatherogenic treatments. VCAM-1 is an adhesion molecule expressed on the activated endothelial surface that binds leucocyte ligands and therefore promotes leucocyte adhesion and transendothelial migration. Hence, for several years, there has been an increase in molecular imaging methods for detecting VCAM-1 in MRI, PET, SPECT, optical imaging and ultrasound. The use of microparticles of iron oxide (MPIO), ultrasmall superparamagnetic iron oxide (USPIO), microbubbles, echogenic immunoliposomes, peptides, nanobodies and other nanoparticles has been described. However, these approaches have been tested in animal models, and the remaining challenge is bench-to-bedside development and clinical applicability.

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Section: Imaging Of Vcam-1mentioning

confidence: 99%

Section: Imaging Of Vcam-1mentioning

confidence: 99%

VCAM-1 Target in Non-Invasive Imaging for the Detection of Atherosclerotic Plaques

Thayse

Kindt

Laurent

et al. 2020

Biology

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“…Thermal unfolding of A1 or C6 was therefore monitored by circular dichroism. A1, C6, and an irrelevant control sdAb were then radiolabeled with 99m Tc using the tricarbonyl method and the C-terminal hexahistidine-tag as previously described (19). The radiochemical purity of all 3 sdAbs was determined immediately after labeling and 6 h after labeling by radio-high-performance liquid chromatography (Shimadzu).…”

Section: Radiolabeling With 99m Tcmentioning

confidence: 99%

Preclinical Evaluation of Mesothelin-Specific Ligands for SPECT Imaging of Triple-Negative Breast Cancer

et al. 2018

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Mesothelin is a cell-surface glycoprotein restricted to mesothelial cells overexpressed in several types of cancer, including triplenegative breast cancer not responding to trastuzumab or hormonebased therapies. Mesothelin-targeting therapies are currently being developed. However, the identification of patients potentially eligible for such a therapeutic strategy remains challenging. The objective of this study was to perform the radiolabeling and preclinical evaluation of 99m Tc-A1 and 99m Tc-C6, two antimesothelin single-domain antibody (sdAb)-derived imaging agents. Methods: A1 and C6 were radiolabeled with 99m Tc and evaluated in vitro on recombinant protein and cells, as well as in vivo in xenograft mouse models of the triplenegative breast cancer cell lines HCC70 (mesothelin-positive) and MDA-MB-231 (mesothelin-negative). Results: Both 99m Tc-A1 and 99m Tc-C6 bound mesothelin with high affinity in vitro, with 99m Tc-A1 affinity being 2.4-fold higher than that of 99m Tc-C6 (dissociation constant, 43.9 ± 4.0 vs. 107 ± 16 nM, P , 0.05). 99m Tc-A1 and 99m Tc-C6 remained stable in vivo in murine blood (.80% at 2 h) and ex vivo in human blood (.90% at 6 h). In vivo 99m Tc-A1 uptake (percentage injected dose) in HCC70 tumors was 5-fold higher than in MDA-MB-231 tumors and 1.5-fold higher than that of 99m Tc-C6 (2.34% ± 0.36% vs. 0.48% ± 0.18% and 1.56% ± 0.43%, respectively, P , 0.01) and resulted in elevated tumor-to-background ratios. In vivo competition experiments demonstrated the specificity of 99m Tc-A1 uptake in HCC70 tumors. Conclusion: Mesothelin-positive tumors were successfully identified by SPECT using 99m Tc-A1 and 99m Tc-C6. Considering its superior characteristics, 99m Tc-A1 was selected as the most suitable tool for further clinical translation.

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“…To assess the role of VCAM-1 in the metastatic phenotype of BC, nuclear imaging may represent a powerful tool. We recently developed a single domain antibody (sdAb)-based radiotracer targeting VCAM-1 called 99m Technetium-cAbVCAM1-5 ( 99m Tc-cAbVCAM1-5), which is ongoing clinical transfer for detection of inflamed atherosclerosis lesions [20,21]. The aim of the present study was to assess VCAM-1 expression using 99m Tc-cAbVCAM1-5 in subcutaneous and lung metastasis mice models of TNBC.…”

Section: Introductionmentioning

confidence: 99%

In Vivo Assessment of VCAM-1 Expression by SPECT/CT Imaging in Mice Models of Human Triple Negative Breast Cancer

Montemagno

Dumas

Cavaillès

et al. 2019

Cancers

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Recent progress in breast cancer research has led to the identification of Vascular Cell Adhesion Molecule-1 (VCAM-1) as a key actor of metastatic colonization. VCAM-1 promotes lung-metastases and is associated with clinical early recurrence and poor outcome in triple negative breast cancer (TNBC). Our objective was to perform the in vivo imaging of VCAM-1 in mice models of TNBC. The Cancer Genomic Atlas (TCGA) database was analyzed to evaluate the prognostic role of VCAM-1 in TNBC. MDA-MB-231 (VCAM-1+) and control HCC70 (VCAM-1-) TNBC cells were subcutaneously xenografted in mice and VCAM-1 expression was assessed in vivo by single-photon emission computed tomography (SPECT) imaging using 99mTc-cAbVCAM1-5. Then, MDA-MB-231 cells were intravenously injected in mice and VCAM-1 expression in lung metastasis was assessed by SPECT imaging after 8 weeks. TCGA analysis showed that VCAM-1 is associated with a poor prognosis in TNBC patients. In subcutaneous tumor models, 99mTc-cAbVCAM1-5 uptake was 2-fold higher in MDA-MB-231 than in HCC70 (p < 0.01), and 4-fold higher than that of the irrelevant control (p < 0.01). Moreover, 99mTc-cAbVCAM1-5 uptake in MDA-MB-231 lung metastases was also higher than that of 99mTc-Ctl (p < 0.05). 99mTc-cAbVCAM1-5 is therefore a suitable tool to evaluate the role of VCAM-1 as a marker of tumor aggressiveness of TNBC.

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Evaluation of Antiatherogenic Properties of Ezetimibe Using ³H-Labeled Low-Density-Lipoprotein Cholesterol and ^99mTc-cAbVCAM1–5 SPECT in ApoE^−/− Mice Fed the Paigen Diet

Cited by 20 publications

References 19 publications

VCAM-1 Target in Non-Invasive Imaging for the Detection of Atherosclerotic Plaques

VCAM-1 Target in Non-Invasive Imaging for the Detection of Atherosclerotic Plaques

Preclinical Evaluation of Mesothelin-Specific Ligands for SPECT Imaging of Triple-Negative Breast Cancer

In Vivo Assessment of VCAM-1 Expression by SPECT/CT Imaging in Mice Models of Human Triple Negative Breast Cancer

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