Novel MRI and fluorescent probes responsive to the Factor XIII transglutaminase activity

Tei, Lorenzo; Mazooz, Galit; Shellef, Yael; Avni, Reut; Vandoorne, Katrien; Kalchenko, Vyacheslav; Dewhirst, Mark W.; Chaabane, Linda; Miragoli, Luigi; Longo, Dario Livio; Neeman, Michal; Aime, Silvio

doi:10.1002/cmmi.392

Cited by 23 publications

(14 citation statements)

References 36 publications

(34 reference statements)

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“…Tissue transglutaminase is highly expressed in certain cancers such as breast cancer and plays a role in cancer cell invasion, metastasis, survival and chemoresistance (Herman, Mangala, & Mehta, 2006; Mangala, et al, 2007). MR contrast agent conjugated to enzyme substrate analogs was applied for molecular imaging of tissue transglutaminase activity (Mazooz, et al, 2005; Tei, et al, 2010). Briefly, low molecular weight tissue transglutaminase substrate analogs, were conjugated to Gd-DTPA and to fluorescent dyes.…”

Section: Targeting the Tumor Stromamentioning

confidence: 99%

Imaging aspects of the tumor stroma with therapeutic implications

Narunsky

Oren

Bochner

et al. 2014

Pharmacology & Therapeutics

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Cancer cells rely on extensive support from the stroma in order to survive, proliferate and invade. The tumor stroma is thus an important potential target for anti-cancer therapy. Typical changes in the stroma include a shift from the quiescence promoting- antiangiogenic extracellular matrix to a provisional matrix that promotes invasion and angiogenesis. These changes in the extracellular matrix are induced by changes in the secretion of extracellular matrix proteins and glucose amino glycans, extravasation of plasma proteins from hyperpermeable vessels and release of matrix modifying enzymes resulting in cleavage and crosslinking of matrix macromolecules. These in turn alter the rigidity of the matrix and the exposure and release of cytokines. Changes in matrix rigidity and vessel permeability affect drug delivery and mediate resistance to cytotoxic therapy. These stroma changes are brought about not only by the cancer cells, but also through the action of many cell types that are recruited by tumors including immune cells, fibroblasts and endothelial cells. Within the tumor, these normal host cells are activated resulting in loss of inhibitory and induction of cancer promoting activities. Key to the development of stroma targeted therapies, selective biomarkers were developed for specific imaging of key aspects of the tumor stroma.

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Section: Targeting the Tumor Stromamentioning

confidence: 99%

Imaging aspects of the tumor stroma with therapeutic implications

Narunsky

Oren

Bochner

et al. 2014

Pharmacology & Therapeutics

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“…Similar results occurred in other studies using Gd-based MR agents conjugated to comparable targeting sequences. 112, 113 …”

Section: Recent Advances In Atherosclerosis Research Have Revealed Nementioning

confidence: 99%

Molecular Imaging of Atherosclerosis for Improving Diagnostic and Therapeutic Development

Quillard

Libby

2012

Circulation Research

109

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Despite recent progress, cardiovascular and allied metabolic disorders remain a worldwide health challenge. We need to identify new targets for therapy, develop new agents for clinical use, and deploy them in a clinically-effective and cost-effective manner. Molecular imaging of atherosclerotic lesions has become a major experimental tool in the last decade, notably by providing a direct gateway to the processes involved in atherogenesis and its complications. This review summarizes the current status of molecular imaging approaches that target the key processes implicated in plaque formation, development, and disruption, and highlights how the refinement and application of such tools might aid the development and evaluation of novel therapeutics.

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“…Transglutaminases are also involved in tumor progression and invasion since they mediate tissue remodeling by catalyzing covalent cross-links between proteins of the ECM (53). Tissue transglutaminase activity has been recently assessed in vivo with MRI by using an imaging probe composed of a peptide DCCP16, extracted from α2-antiplasmin, the primary inhibitor of plasmin-mediated fibrinolysis.…”

Section: Probes For Imaging the Physiological Environment The Extracmentioning

confidence: 99%

“…Tissue transglutaminase activity has been recently assessed in vivo with MRI by using an imaging probe composed of a peptide DCCP16, extracted from α2-antiplasmin, the primary inhibitor of plasmin-mediated fibrinolysis. The peptide was linked to an imaging reporter labeled with Gd-DOTA that was visible on T 1 -weighted images (53). The probe was tested in vivo in a model of 4T1 mammary gland tumor, 24 h after injection, retention of the transglutaminase-targeted probe was observed in the tumor, that was not the case for the negative control probe.…”

Section: Probes For Imaging the Physiological Environment The Extracmentioning

confidence: 99%

“…The peptidic moiety present on the probe served as a transglutaminase substrate analog, and thus allowed the binding of the probe on transglutaminase present in the tumor, allowing its detection by MRI. Noninvasive imaging of transglutaminase activity by MRI can provide an important tool for monitoring transglutaminase-targeted therapy (53). …”

Section: Probes For Imaging the Physiological Environment The Extracmentioning

confidence: 99%

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MR – eyes for cancer: looking within an impenetrable disease

et al. 2013

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Probe development is a critical component in cancer imaging, and novel probes are making major inroads in several aspects of cancer detection and image-guided treatments. Intrinsic MR probes such as signals from metabolites and their chemical shifts have been used for more than a decade to understand cancer physiology and metabolism. Through the integration of technology, molecular biology, and chemistry, the last few years have witnessed an explosion of extrinsic probes for molecular and functional imaging of cancer that, together with techniques such as CEST and hyperpolarization, have significantly expanded the repertoire of MR techniques in basic and translational investigations of many different aspects of cancer. Furthermore, incorporation of MR probes into multifunctional nanoparticles and multimodality imaging platforms have opened new opportunities for MR in image-guided diagnosis and therapy of cancer. Here we have provided an overview of recent innovations that have occurred in the development of MRI probes for molecular and functional imaging of cancer. Although most of these novel probes are not clinically available, they offer significant promise for future translational applications. In this review, we have highlighted the areas of future development that are likely to have a profound impact on cancer detection and treatment.

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Novel MRI and fluorescent probes responsive to the Factor XIII transglutaminase activity

Cited by 23 publications

References 36 publications

Imaging aspects of the tumor stroma with therapeutic implications

Imaging aspects of the tumor stroma with therapeutic implications

Molecular Imaging of Atherosclerosis for Improving Diagnostic and Therapeutic Development

MR – eyes for cancer: looking within an impenetrable disease

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