Imaging the Alternatively Spliced D Domain of Tenascin C in Preclinical Models of Inflammatory Bowel Disease

Purpose To image colon-expressed alternatively spliced D domain of tenascin C in preclinical colitis models using near infrared (NIR) labeled targeted molecular imaging agents.Methods Human IgG and scFv fusion proteins specific to the alternatively spliced D domain of tenascin C were generated. Immunohistochemistry identified disease-specific expression of this extracellular matrix in mouse colitis models. Proteins were labeled with the NIR fluorophore IRDye 800CW via amine chemistry and intravenously dosed to evaluate targeting specificity in preclinical rodent and primate colitis models.Results The NIR labeled proteins successfully targeted colonic lesions in a murine model of colitis and appeared as distinct punctate spots. Co-administration of a blocking dose reduced the whole colon standardized uptake of the fluorescent dose >7-fold in mouse models. Estimates suggest local expression at >100 nM in diseased mouse colon. Macroscopic targeting specificity was not observed in diseased primate colon. Cellular level specificity was assessed via microscopy and immunohistochemistry.Conclusion Our imaging data suggest the alternatively spliced D domain of tenascin C is a promising target for delivery-based applications in inflammatory bowel diseases.

A Nano-Emulsion Platform Functionalized with a Fully Human scFv-Fc Antibody for Atheroma Targeting: Towards a Theranostic Approach to Atherosclerosis

Atherosclerosis is at the onset of the cardiovascular diseases that are among the leading causes of death worldwide. Currently, high-risk plaques, also called vulnerable atheromatous plaques, remain often undiagnosed until the occurrence of severe complications, such as stroke or myocardial infarction. Molecular imaging agents that target high-risk atheromatous lesions could greatly improve the diagnosis of atherosclerosis by identifying sites of high disease activity. Moreover, a “theranostic approach” that combines molecular imaging agents (for diagnosis) and therapeutic molecules would be of great value for the local management of atheromatous plaques. The aim of this study was to develop and characterize an innovative theranostic tool for atherosclerosis. We engineered oil-in-water nano-emulsions (NEs) loaded with superparamagnetic iron oxide (SPIO) nanoparticles for magnetic resonance imaging (MRI) purposes. Dynamic MRI showed that NE-SPIO nanoparticles decorated with a polyethylene glycol (PEG) layer reduced their liver uptake and extended their half-life. Next, the NE-SPIO-PEG formulation was functionalized with a fully human scFv-Fc antibody (P3) recognizing galectin 3, an atherosclerosis biomarker. The P3-functionalized formulation targeted atheromatous plaques, as demonstrated in an immunohistochemistry analyses of mouse aorta and human artery sections and in an Apoe−/− mouse model of atherosclerosis. Moreover, the formulation was loaded with SPIO nanoparticles and/or alpha-tocopherol to be used as a theranostic tool for atherosclerosis imaging (SPIO) and for delivery of drugs that reduce oxidation (here, alpha-tocopherol) in atheromatous plaques. This study paves the way to non-invasive targeted imaging of atherosclerosis and synergistic therapeutic applications.

Radiolabeled curcumin as β amyloid imaging and tumor targeting imaging agents

Curcumin, a polyphenolic compound, derived from the rhizomes of Curcuma longa L. Curcumin shows potential pharmacological action against numerous disorders, including cancer, neurodegenerative, and infection diseases. Curcumin-based molecular imaging agents could be useful for early detection of Alzheimer Disease and tumor and monitor the progress of therapy. Radiolabeled curcumin and its derivatives become promising compounds as imaging agents. In this review, radiolabeled curcumin bearing radionuclides including fluorine-18, Technetium-99m, Iodine-125, and Gallium-68 are reviewed as an effort to develop curcumin-based probes not only for β amyloid imaging but also for tumor imaging.

Radiomics, aptamers and nanobodies: New insights in cancer diagnostics and imaging

At present, cancer is a major health issue and the second leading cause of mortality worldwide. Researchers have been working hard on investigating not only improved therapeutics but also on early detection methods, both critical to increasing treatment efficacy and developing methods for disease prevention. Diagnosis of cancers at an early stage can promote timely medical intervention and effective treatment and will result in inhibiting tumor growth and development. Several advances have been made in the diagnostics and imagining technologies for early tumor detection and deciding an effective therapy these include radiomics, nanobodies, and aptamers. Here in this review, we summarize the main applications of radiomics, aptamers, and the use of nanobody-based probes for molecular imaging applications in diagnosis, treatment planning, and evaluations in the field of oncology to develop quantitative and personalized medicine. The preclinical data reported to date are quite promising, and it is predicted that nanobody-based molecular imaging agents will play an important role in the diagnosis and management of different cancer types in near future.

Expanding the Chemistry Palette for Radiotracer Synthesis

The synthesis, characterisation and application of radiolabelled compounds for use in diagnostic and therapeutic medicine requires a diverse skill set. This article highlights a selection of our ongoing projects that aim to provide new synthetic methods and radiochemical tools for building molecular imaging agents with various radionuclides.