Nanobodies as Versatile Tool for Multiscale Imaging Modalities

Molecular imaging is constantly growing in different areas of preclinical biomedical research. Several imaging methods have been developed and are continuously updated for both in vivo and in vitro applications, in order to increase the information about the structure, localization and function of molecules involved in physiology and disease. Along with these progresses, there is a continuous need for improving labeling strategies. In the last decades, the single domain antigen-binding fragments nanobodies (Nbs) emerged as important molecular imaging probes. Indeed, their small size (~15 kDa), high stability, affinity and modularity represent desirable features for imaging applications, providing higher tissue penetration, rapid targeting, increased spatial resolution and fast clearance. Accordingly, several Nb-based probes have been generated and applied to a variety of imaging modalities, ranging from in vivo and in vitro preclinical imaging to super-resolution microscopy. In this review, we will provide an overview of the state-of-the-art regarding the use of Nbs in several imaging modalities, underlining their extreme versatility and their enormous potential in targeting molecules and cells of interest in both preclinical and clinical studies.

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Multimodal Imaging Probe for Melanoma Evaluating of PTK7 Expression by Sgc8-c Aptamer Recognition

10.21203/rs.3.rs-200306/v1 ◽

2021 ◽

Author(s):

Estefanía Sicco ◽

Amy Mónaco ◽

Marcelo Fernandez ◽

María Moreno ◽

Victoria Calzada ◽

...

Keyword(s):

Molecular Imaging ◽

Dna Aptamer ◽

Specific Expression ◽

Imaging Probe ◽

Molecular Imaging Probes ◽

Imaging Probes ◽

Diagnosis Of Cancer ◽

Animal Tumor

Abstract Melanoma is one of the most aggressive and deadly skin cancers, and although histopathological criteria are used for its prognosis, biomarkers are necessary to identify the different evolution stages. The applications of molecular imaging include the in vivo diagnosis of cancer with probes that recognize the tumor-biomarkers specific expression allowing external images acquisitions and evaluations of the biological process in quali-quantitative ways. Aptamers are oligonucleotides that recognize targets with high affinity and specificity presenting advantages that make them interesting molecular imaging probes. Sgc8-c (DNA-aptamer) selectively recognizes PTK7-receptor overexpressed in various types of tumors. Herein, Sgc8-c was evaluated, in two melanoma models, non-metastatic and metastatic, as molecular imaging probe for in vivo diagnostic. Firstly, two probes, radio- and fluorescent-probe, were in vitro evaluated verifying the high specific PTK7 recognition and its internalization in tumor cells by the endosomal route. Secondly, in vivo proof of concept was performed in animal tumor models. Likewise, they have rapid clearance from blood exhibiting excellent target (tumor)/non-target organ ratios. Furthermore, optimal biodistribution was observed 24 hours after probes-injections accumulating almost exclusively in the tumor tissue. Sgc8-c is a potential tool for their specific use in the early detection of melanoma.

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Metastatic and non-metastatic melanoma imaging using Sgc8-c aptamer PTK7-recognizer

Scientific Reports ◽

10.1038/s41598-021-98828-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Estefanía Sicco ◽

Amy Mónaco ◽

Marcelo Fernandez ◽

María Moreno ◽

Victoria Calzada ◽

...

Keyword(s):

Molecular Imaging ◽

Metastatic Melanoma ◽

Dna Aptamer ◽

Specific Expression ◽

Molecular Imaging Probes ◽

Imaging Probes ◽

Melanoma Model ◽

In Vivo Diagnosis

AbstractMelanoma is one of the most aggressive and deadly skin cancers, and although histopathological criteria are used for its prognosis, biomarkers are necessary to identify the different evolution stages. The applications of molecular imaging include the in vivo diagnosis of cancer with probes that recognize the tumor-biomarkers specific expression allowing external image acquisitions and evaluation of the biological process in quali-quantitative ways. Aptamers are oligonucleotides that recognize targets with high affinity and specificity presenting advantages that make them interesting molecular imaging probes. Sgc8-c (DNA-aptamer) selectively recognizes PTK7-receptor overexpressed in various types of tumors. Herein, Sgc8-c was evaluated, for the first time, in a metastatic melanoma model as molecular imaging probe for in vivo diagnostic, as well as in a non-metastatic melanoma model. Firstly, two probes, radio- and fluorescent-probe, were in vitro evaluated verifying the high specific PTK7 recognition and its internalization in tumor cells by the endosomal route. Secondly, in vivo proof of concept was performed in animal tumor models. In addition, they have rapid clearance from blood exhibiting excellent target (tumor)/non-target organ ratios. Furthermore, optimal biodistribution was observed 24 h after probes injections accumulating almost exclusively in the tumor tissue. Sgc8-c is a potential tool for their specific use in the early detection of melanoma.

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Recent advances in molecular imaging probes for β-amyloid plaques

MedChemComm ◽

10.1039/c4md00365a ◽

2015 ◽

Vol 6 (3) ◽

pp. 391-402 ◽

Cited By ~ 36

Author(s):

Masahiro Ono ◽

Hideo Saji

Keyword(s):

Molecular Imaging ◽

Optical Imaging ◽

Amyloid Plaques ◽

Recent Advances ◽

Molecular Imaging Probes ◽

Imaging Probes ◽

Β Amyloid ◽

The Brain

We review recent advances in our development of molecular imaging probes for PET, SPECT, and optical imaging for in vivo detection of β-amyloid plaques in the brain.

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Radiolabeled Molecular Imaging Probes for the In Vivo Evaluation of Cellulose Nanocrystals for Biomedical Applications

Biomacromolecules ◽

10.1021/acs.biomac.8b01313 ◽

2018 ◽

Vol 20 (2) ◽

pp. 674-683 ◽

Cited By ~ 9

Author(s):

Surachet Imlimthan ◽

Sofia Otaru ◽

Outi Keinänen ◽

Alexandra Correia ◽

Kalle Lintinen ◽

...

Keyword(s):

Molecular Imaging ◽

Cellulose Nanocrystals ◽

Biomedical Applications ◽

In Vivo Evaluation ◽

Molecular Imaging Probes ◽

Imaging Probes

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Mitochondrial-Targeted Molecular Imaging in Cardiac Disease

BioMed Research International ◽

10.1155/2017/5246853 ◽

2017 ◽

Vol 2017 ◽

pp. 1-11 ◽

Cited By ~ 1

Author(s):

Jinhui Li ◽

Jing Lu ◽

You Zhou

Keyword(s):

Molecular Imaging ◽

Cardiac Disease ◽

Single Photon ◽

Photon Emission ◽

Emission Computed Tomography ◽

Positron Emission ◽

Molecular Imaging Probes ◽

Imaging Probes ◽

Targeted Molecular Imaging

The present study aimed to discuss the role of mitochondrion in cardiac function and disease. The mitochondrion plays a fundamental role in cellular processes ranging from metabolism to apoptosis. The mitochondrial-targeted molecular imaging could potentially illustrate changes in global and regional cardiac dysfunction. The collective changes that occur in mitochondrial-targeted molecular imaging probes have been widely explored and developed. As probes currently used in the preclinical setting still have a lot of shortcomings, the development of myocardial metabolic activity, viability, perfusion, and blood flow molecular imaging probes holds great potential for accurately evaluating the myocardial viability and functional reserve. The advantages of molecular imaging provide a perspective on investigating the mitochondrial function of the myocardium in vivo noninvasively and quantitatively. The molecular imaging tracers of single-photon emission computed tomography and positron emission tomography could give more detailed information on myocardial metabolism and restoration. In this study, series mitochondrial-targeted99mTc-,123I-, and18F-labeled tracers displayed broad applications because they could provide a direct link between mitochondrial dysfunction and cardiac disease.

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Minireview: Nanoparticles for Molecular Imaging—An Overview

Endocrinology ◽

10.1210/en.2009-1012 ◽

2010 ◽

Vol 151 (2) ◽

pp. 474-481 ◽

Cited By ~ 80

Author(s):

Rodney F. Minchin ◽

Darren J. Martin

Keyword(s):

Molecular Imaging ◽

Human Disease ◽

Disease Diagnosis ◽

Imaging Modalities ◽

Biological Processes ◽

Physiological Changes ◽

Field Of Study ◽

Imaging Probes ◽

Experimental Stage

Molecular imaging is a technique for quantifying physiological changes in vivo using imaging probes, or beacons, which can be detected noninvasively. This field of study has advanced rapidly in recent years, in part due to the application of nanotechnology. The versatility of different imaging modalities has been significantly enhanced by innovative nanoparticle development. These nanoprobes can be used to image specific cells and tissues within a whole organism. Some of the nanoparticles under development may be useful to measure biological processes associated with human disease and help monitor how these change with treatment. This review highlights some of the recent advances in nanoparticles for molecular imaging. It also addresses issues that arise with the use of nanoparticles. Whereas much of the technology remains at an experimental stage, the potential for enhancing disease diagnosis and treatment is considerable.

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Molecular Imaging Probes for Diagnosis and Therapy Evaluation of Breast Cancer

International Journal of Biomedical Imaging ◽

10.1155/2013/230487 ◽

2013 ◽

Vol 2013 ◽

pp. 1-14 ◽

Cited By ~ 14

Author(s):

Qingqing Meng ◽

Zheng Li

Keyword(s):

Breast Cancer ◽

Molecular Imaging ◽

Cancer Biology ◽

Hormone Receptors ◽

Receptor Imaging ◽

Therapy Evaluation ◽

Diagnosis And Therapy ◽

Molecular Imaging Probes ◽

Imaging Probes

Breast cancer is a major cause of cancer death in women where early detection and accurate assessment of therapy response can improve clinical outcomes. Molecular imaging, which includes PET, SPECT, MRI, and optical modalities, provides noninvasive means of detecting biological processes and molecular eventsin vivo.Molecular imaging has the potential to enhance our understanding of breast cancer biology and effects of drug action during both preclinical and clinical phases of drug development. This has led to the identification of many molecular imaging probes for key processes in breast cancer. Hormone receptors, growth factor receptor, and angiogenic factors, such as ER, PR, HER2, and VEGFR, have been adopted as imaging targets to detect and stage the breast cancer and to monitor the treatment efficacy. Receptor imaging probes are usually composed of targeting moiety attached to a signaling component such as a radionuclide that can be detected using dedicated instruments. Current molecular imaging probes involved in breast cancer diagnosis and therapy evaluation are reviewed, and future of molecular imaging for the preclinical and clinical is explained.

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Abstract 1454: Targeted Molecular Imaging Probes For In Vivo MR Detection Of Atherosclerotic Lesions Using Antibodies Against Oxidized Low Density Lipoprotein

Circulation ◽

10.1161/circ.116.suppl_16.ii_299-b ◽

2007 ◽

Vol 116 (suppl_16) ◽

Author(s):

Karen C Briley-Saebo ◽

Willem Mulder ◽

Peter X Shaw ◽

Seung-Hyuk Choi ◽

Venkatesh Mani ◽

...

Keyword(s):

Molecular Imaging ◽

Mr Imaging ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Low Density ◽

Oxidized Low Density Lipoprotein ◽

Atherosclerotic Lesions ◽

Molecular Imaging Probes ◽

Imaging Probes

Background: Oxidized low-density lipoprotein (OxLDL) plays a key role in the initiation, progression and destabilization of atherosclerotic plaque. Molecular imaging probes that target OxLDL may allow in vivo detection of vulnerable plaques. In this study, magnetic resonance imaging (MRI) was used to detect atherosclerotic lesions in apolipoprotein deficient mice (ApoE−/−) using micelles comprised of gadolinium lipids, fluorescent rhodamine, PEG-lipids, and MDA2, a murine monoclonal antibody that binds malondialdehyde (MDA) lysine epitopes present in OxLDL. Materials and Results: Untargeted micelles, MDA2-labeled micelles and nonspecific polyclonal IgG micelles were prepared and characterized with respect to OxLDL binding capacity, pharmacokinetics, and biodistribution in wild type (WT) and ApoE−/− mice. MR imaging was performed at 9.4T over a 3-week interval after administration of 0.075 mmol Gd/kg micelles. MDA2 increased the micelle size, blood half-life, and MR efficacy relative to untargeted and IgG-micelles. Maximal plaque enhancement (>125%) was observed 72 hours post MDA2-micelle injection (Figure ). Untargeted and IgG-micelles did not exhibit significant wall enhancement at any of the time points studied. Confocal microscopy revealed that MDA2-micelles accumulate within foam cells associated with atherosclerotic plaque. WT mice showed no significant MR wall enhancement for any of the micelles studied. Conclusions: MR imaging using MDA2-micelles demonstrates specific targeting of OxLDL and foam cells and provides excellent MR image quality. This study suggests that it may be feasible to image similar atherosclerotic lesions in humans with MRI.

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