Developments in single photon emission computed tomography and PET-based HER2 molecular imaging for breast cancer

Goldstein, Robert M.; Sosabowski, Jane; Vigor, Kim; Chester, Kerry; Meyer, Tim

doi:10.1586/era.13.11

Cited by 22 publications

(17 citation statements)

References 84 publications

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“…Due to their high specificity, antibodies represent attractive agents for use in diagnostic imaging. However, their prolonged in vivo persistence results in high levels of background and can also induce off-target tissue damage (Goldstein et al, 2013; Jaggi et al, 2007; Wu, 2014). The delivery of an Fc-engineered inhibitor (Abdeg) following the loading of tumor with radiolabeled antibody results in significant improvements in contrast during positron emission tomography [PET (Swiercz et al, 2014)].…”

Section: Modulating Igg Dynamics By Fcrn Inhibitionmentioning

confidence: 99%

Targeting FcRn for the modulation of antibody dynamics

Ward

Devanaboyina

Ober

2015

Molecular Immunology

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The MHC Class I-related receptor, FcRn, is a multitasking protein that transports its IgG ligand within and across cells of diverse origins. The role of this receptor as a global regulator of IgG homeostasis and transport, combined with knowledge of the molecular details of FcRn-IgG interactions, has led to opportunities to modulate the in vivo dynamics of antibodies and their antigens through protein engineering. Consequently, the generation of half-life extended antibodies has shown a rapid expansion over the past decade. Further, FcRn itself can be targeted by inhibitors to induce decreased levels of circulating IgGs, which could have applications in multiple clinical settings. The engineering of antibody-antigen interactions to reduce antibody-mediated buffering of soluble ligand has also developed into an active area of investigation, leading to novel antibody platforms designed to lead to more effective antigen clearance. Similarly, the target-mediated elimination of antibodies by internalizing, membrane bound antigens (receptors) can be decreased using novel engineering approaches. These strategies, combined with subcellular trafficking analyses of antibody/antigen/FcRn behavior in cells to predict in vivo behavior, have considerable promise for the production of next generation therapeutics and diagnostics.

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Section: Modulating Igg Dynamics By Fcrn Inhibitionmentioning

confidence: 99%

Targeting FcRn for the modulation of antibody dynamics

Ward

Devanaboyina

Ober

2015

Molecular Immunology

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“…However, the long in vivo half-lives of antibodies result in high background levels, poor contrast, and radiation exposure of normal tissue (1–3). These problems are exacerbated when the tumor burden is low.…”

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confidence: 99%

Use of Fc-Engineered Antibodies as Clearing Agents to Increase Contrast During PET

et al. 2014

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Despite promise for the use of antibodies as molecular imaging agents in PET, their long in vivo half-lives result in poor contrast and radiation damage to normal tissue. This study describes an approach to overcome these limitations. Methods Mice bearing human epidermal growth factor receptor type 2 (HER2)–overexpressing tumors were injected with radiolabeled (124I, 125I) HER2-specific antibody (pertuzumab). Pertuzumab injection was followed 8 h later by the delivery of an engineered, antibody-based inhibitor of the receptor, FcRn. Biodistribution analyses and PET were performed at 24 and 48 h after pertuzumab injection. Results The delivery of the engineered, antibody-based FcRn inhibitor (or Abdeg, for antibody that enhances IgG degradation) results in improved tumor-to-blood ratios, reduced systemic exposure to radiolabel, and increased contrast during PET. Conclusion Abdegs have considerable potential as agents to stringently regulate antibody dynamics in vivo, resulting in increased contrast during molecular imaging with PET.

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“…In our last study, however, we observed specific binding of the tricine-coliganded labelled aptamer to the HER2 receptor, it did not accumulate in the tumour in vivo [16]. Several monoclonal antibodies and peptides are used as HER2-specific binding molecules for therapy and imaging in preclinical and clinical studies [20][21][22][23], but there are few reports on the use of an aptamer for the imaging of HER2-related cancers. A coligand is needed for radiolabelling the HYNIC conjugate molecule with 99m Tc [24].…”

Section: Discussionmentioning

confidence: 81%

An improved radiolabelled RNA aptamer molecule for HER2 imaging in cancers

Varmira

Hosseinimehr

Noaparast

et al. 2013

Journal of Drug Targeting

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Human epidermal growth factor receptor 2 (HER2) expression has been shown to be increased in several types of human tumours. In this study, for the imaging of HER2-related tumours, a modified RNA aptamer with HER2-specific targeting was labelled with (99m)Tc, by using hydrazino nicotinamide (HYNIC) as the chelator in the presence of tricine or ethylenediamine-N,N'-diacetic acid (EDDA) as the co-ligand. Stability testing of the radiolabelled aptamers in the serum was performed through SDS-PAGE. The aptamer-radionuclide conjugate was evaluated for its cellular HER2-specific binding in ovarian cancer cells (SKOV-3), and its biodistribution properties were assessed in normal and SKOV-3 tumour-bearing mice. In the presence of either tricine or EDDA, the HYNIC-RNA aptamers were labelled with (99m)Tc at a high yield and radiochemical purity. Cellular experiments confirmed the specific binding of the RNA aptamer to the HER2 receptor. In the animal biodistribution study, uptake of the EDDA-co-liganded (99m)Tc-HYNIC-RNA aptamer by the liver and spleen was remarkably lower than that of the aptamer with tricine. Tumours also showed a higher accumulation of radioactivity with the EDDA-co-liganded aptamer complex. This study demonstrated EDDA to be better than tricine for use as a co-ligand with the RNA aptamer, which can be a potential tool for the molecular imaging of HER2-overexpressing cancers.

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Developments in single photon emission computed tomography and PET-based HER2 molecular imaging for breast cancer

Cited by 22 publications

References 84 publications

Targeting FcRn for the modulation of antibody dynamics

Targeting FcRn for the modulation of antibody dynamics

Use of Fc-Engineered Antibodies as Clearing Agents to Increase Contrast During PET

An improved radiolabelled RNA aptamer molecule for HER2 imaging in cancers

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