Targeting vascular endothelium with avidin microbubbles. Ultrasound Med Biol 31, 1279-1283

Hamon Center for Therapeutic Oncology Research, Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Ultrasound in Medicine & Biology (Impact Factor: 2.21). 10/2005; 31(9):1279-83. DOI: 10.1016/j.ultrasmedbio.2005.06.001
Source: PubMed

ABSTRACT Targeting microbubbles (MBs) to specific vascular beds enables contrast ultrasound to be used for molecular imaging. There are several methods for attaching targeting moieties to the surface of MBs. In the present study, we demonstrate that avidin (Av) can be incorporated into the shell of perfluorocarbon-exposed sonicated dextrose albumin (PESDA) MBs (Av-PESDA-MBs) and serve as an anchor that links Av-PESDA-MBs to biotinylated monoclonal antibodies (mAbs). This novel linking strategy was used to conjugate Av-PESDA-MBs to mAbs specific for endoglin (CD105) or a control IgG. MBs targeted to CD105 specifically bound to endothelial cells, but not to fibroblasts, in vitro but Av-PESDA-MBs conjugated with the control IgG did not specifically target either cell type. We conclude that Av-PESDA-MBs represent a novel and attractive tool to conjugate MBs with biotinylated mAbs for the purposes of vascular targeting and molecular imaging.

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    • "Am J Transl Res 2012;4(3):333-346 quantitative and whole-body readout of CD105 expression level in all tumors, which can facilitate lesion detection, patient stratification, anticancer drug development, and personalized therapies. However, molecular imaging of CD105 expression is understudied to date, and the available literature reports are all based on labeled anti-CD105 antibodies [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] [23]. "
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    ABSTRACT: CD105 (endoglin) is an independent marker for poor prognosis in more than 10 solid tumor types. The goal of this study was to develop a CD105-specific agent for both positron emission tomography (PET) and near-infrared fluorescence (NIRF) imaging, which has potential clinical applications in the diagnosis and imaged-guided resection of solid tumors. TRC105, a chimeric anti-CD105 monoclonal antibody, was conjugated to a NIRF dye (800CW) and p-isothiocyanatobenzyl-desferrioxamine (Df-Bz-NCS) before (89)Zr-labeling. Another chimeric antibody, cetuximab, was used as an isotype-matched control. FACS analysis revealed no difference in CD105 binding affinity/specificity between TRC105 and Df-TRC105-800CW. Serial PET imaging revealed that the 4T1 tumor uptake of (89)Zr-Df-TRC105-800CW was 6.3 ± 1.9, 12.3 ± 1.3, and 11.4 ± 1.1 %ID/g at 4, 24, and 48 h post-injection (p.i.) respectively (n = 3), higher than all organs starting from 24 h p.i., which provided excellent tumor contrast. Tumor uptake as measured by both in vivo and ex vivo NIRF imaging had a linear correlation with the %ID/g values obtained from PET, corroborated by biodistribution studies. Blocking experiments, control studies with (89)Zr-Df-cetuximab-800CW, and histology all confirmed the CD105 specificity of (89)Zr-Df-TRC105-800CW. In conclusion, herein we report dual-modality PET and NIRF imaging of CD105 expression in a breast cancer model, where CD105-specific uptake of (89)Zr-Df-TRC105-800CW in the tumor was observed.
    American Journal of Translational Research 08/2012; 4(3):333-46. · 3.40 Impact Factor
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    • "Albumin-shelled MBs and a paramagnetic-labeled macromolecule, albumin(Gd-DTPA ), are used as US and MRI contrast agents, respectively [4] [5]. Some studies have found that local inflammation and angiogenesis can be detected by incorporating the targeting ligands in albumin-shelled MBs [6]. Moreover, some drugs have been encapsulated in albumin microspheres [7]. "
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    ABSTRACT: OBJECTIVE: In this study, albumin-shelled, targeted MBs (tMBs) were first demonstrated with the expectation of visualization of biodistribution of albumin-shelled tMBs. The actual biodistribution of albumin-shelled tMBs is of vital importance either for molecular imaging or for drug delivery. MOTIVATION: Recently, albumin microbubbles (MBs) have been studied for drug and gene delivery in vitro and in vivo through cavitation. Targeted lipid-shelled MBs have been applied for ultrasound molecular imaging and conjugated with radiolabeled antibodies for whole-body biodistribution evaluations. The novelty of the work is that, in addition to the lipid tMBs, the albumin tMBs was also applied in biodistribution detection. METHODS: Multimodality albumin-shelled, (18)F-SFB-labeled VEGFR2 tMBs were synthesized, and their characteristics in mice bearing MDA-MB-231 human breast cancer were investigated with micro-positron-emission tomography (microPET) and high-frequency ultrasound (microUS). RESULTS: Albumin-shelled MBs can be labeled with (18)F-SFB directly and conjugated with antibodies for dual molecular imaging. The albumin-shelled tMBs show a lifetime in 30min in the blood pool and a highly specific adherence to tumor vessels in mice bearing human breast cancer. CONCLUSIONS: From the evaluations of whole-body biodistribution, the potential of the dual molecular imaging probe for drug or gene delivery in animal experiments with albumin shelled MBs has been investigated.
    Ultrasonics 07/2012; 53(2). DOI:10.1016/j.ultras.2012.06.014 · 1.94 Impact Factor
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    • "In one study, avidin (Av) was incorporated into the shell of perfluorocarbon-exposed sonicated dextrose albumin microbubbles (Av-MBs) to anchor biotinylated monoclonal antibodies (mAbs) [35]. A rat anti-mouse CD105 mAb (MJ7/18) and an isotype-matched control mAb were investigated for biotinylation, microbubble incorporation , and cellular studies. "
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    ABSTRACT: Since most solid tumor growth depends on angiogenesis, non-invasive imaging of tumor angiogenesis can allow for much earlier diagnosis and better prognosis of cancer, as well as more accurate treatment monitoring, which will eventually lead to personalized molecular medicine. CD105, also known as endoglin, is required for endo-thelial cell proliferation. The currently accepted standard method for quantifying tumor angiogenesis is to assess microvessel density based on CD105 staining, which has been shown to be an independent prognostic factor for survival in patients of almost all solid tumor types. In this review, we will summarize the progress to date on multimo-dality molecular imaging of CD105 expression during tumor angiogenesis which includes targeted contrast-enhanced ultrasound, molecular magnetic resonance, near-infrared fluorescence, single-photon emission computed tomography, and positron emission tomography. Although molecular imaging of CD105 expression is surprisingly understudied, non-invasive imaging of CD105 expression has already been achieved with every single molecular imaging modality. In the future, significant research effort should be directed towards non-invasive visualization of CD105 expression, such as quantitative imaging, the use of long-lived isotopes for antibody-based imaging, development of peptide, small molecule, or antibody fragment-based imaging agents, multimodality imaging of CD105 expression with a single agent, the application of nanotechnology, among others.
    International Journal of Clinical and Experimental Medicine 01/2011; 4(1):32-42. · 1.28 Impact Factor
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