Diazaborines Oxidize Slowly with H2O2 but Rapidly with Peroxynitrite in Aqueous Buffer

Reactive oxygen species (ROS) such as H2O2 and peroxynitrite (ONOO-) oxidize arylboronic acids to their corresponding phenols. When used in molecular imaging probes and in ROS-responsive molecules, however, simple arylboronic...

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

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 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.

Early Detection of Tau Pathology

While a definitive Alzheimer's disease (AD) diagnosis remains a post-mortem exercise, the ATN Research Framework proposed by the National Institute on Aging and the Alzheimer's Association utilizes a score representing the presence of amyloid deposits (A), tau deposits (T) and neuronal degeneration markers (N), with A+T+ necessary for a positive diagnosis. Current detection of tau pathology lags amyloid detection by years and by the time both markers are detected the disease is fairly advanced. We describe the development of a new generation of molecular imaging probes for in vivo detection of cells undergoing abnormal phosphorylation representing the initial stages of pTau pathology, potentially enabling a very early stage diagnosis of AD. We describe a novel nanoparticle formulation that binds such abnormally phosphorylating cells in a mouse model of tau pathology, enabling in vivo visualization of the hyperphosphorylative state by magnetic resonance imaging. Our results demonstrate the potential of this novel platform to identify a correlative marker signifying the development of future tau pathology, and has implications for early-stage diagnosis of Alzheimer's disease.

RHAMM-Target Peptides as Molecular Imaging Probes for the Imaging of RHAMM-Expressing Cancer Cells

The incidence of cancer in the world is growing steadily. Therefore, it is necessary to develop new approaches for the early diagnosis of cancer. This work is devoted to the study of the potential of RHAMM-target peptides for molecular diagnosis of cancer. The key amino acids of the RHAMM target peptides were identified by the alanine scan method. The specificity of binding of peptides to RHAMM-CT was assessed using competitive HA substitution by the ELISA method. RHAMM-CT was obtained by genetic engineering and isolated by affinity chromatography. The interaction of RHAMM target peptides with the surface receptor of tumor cells was evaluated by confocal microscopy. It has been shown that fragment EEGEEZ in the peptides' composition is necessary for binding to the RHAMM-CT. The results showed that the RHAMM-target peptides bind specifically to the RHAMM-CT and competitively substituted HA at the RHAMM. It has been found that aggrecan is unable to displace peptides from the HA binding site of RHAMM-CT. The results showed that the FITC peptide binds specifically to RHAMM on the surface of prostate cancer cells. Therefore, RHAMM-target peptides have the potential for early molecular diagnosis of cancer.

Nanotechnology for Molecular Imaging of Atherosclerosis: Current Design and Approaches

Atherosclerosis complications such as myocardial infarction or stroke is still one of the most critical causes of death worldwide. Advance and innovative diagnostic technologies are urgently required to discover an early stage of the disease, such as plaque instability and thrombosis. A combination of molecular imaging probes based on well-designed nanomaterials with leading-edge imaging methods is currently concreting the direction for novel and distinctive approaches to examine the inflammatory growth in atherosclerosis. Over the past several decades, an exceptional understanding of the biological nature of atherosclerosis provides unique opportunities to better treat atherosclerotic disease with targeted imaging and nanomedicines. Consequently, tremendous development has been initiated in the nanotechnology application; the leading engineering tools working at molecular range, which is designed for diagnostic and therapeutic approach, called theranostic. This review underlying ideas involving the potential and development of molecular imaging technologies that had been invented for studying atherosclerosis. We envisage that many molecular imaging methods will become valuable assistants to the clinical management of targeted treatment in the atherosclerosis disease together with their challenges and future perspective in clinical translation.

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

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.

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.