Molecular magnetic resonance imaging for tumour targeting

During my postgraduate training in Radiology at the University of Genoa, Italy, I developed research projects on the application of molecular magnetic resonance imaging for tumour targeting. Molecular imaging (MI) aims to provide “pictures of what is happening inside the body at molecular and cellular level”. Magnetic resonance imaging (MRI) has been applied to many aspects of MI. Although it offers better temporal and spatial resolution than other methodologies, it is less sensitive for molecular or cellular activities, and therefore there is a need to develop more efficient contrast agents. The publications included in this PhD thesis demonstrate the successful application of two classes of MRI contrast agents: ultrasmall superparamagnetic iron oxide nanoparticles (USPIO) and manganese (Mn2+). Novel USPIO-antibody-conjugated probes for investigating lymphoma tumours were applied, and the potential of labelling natural killer cells by SPIO was demonstrated, offering a great opportunity for in vivo investigation of these lymphocytes that play an essential role in cell-based immune defence. The development of a birdcage prototype coil for a clinical 3T MR scanner with a commercial scientific collaboration was carried out. Research projects for investigating tumour calcium metabolism and risk of bone metastases were developed preclinically (by using Mn2+ in human preclinical cancer animal models) and clinically (by using in vivo proton magnetic resonance spectroscopy to investigate human breast cancer). An in vivo Manganese-enhanced-MRI (MEMRI) technique to visualise brown adipose tissue, its physiopathology, and its role in breast or prostate cancer progression, has been included as well. The last research projects carried out as the conclusion of this PhD were focused on: 1) the development of a novel USPIO-MR imaging approach to monitor chronic lymphocytic leukaemia (CLL), induced by interfering with both miR-15 and miR-16 expression; and 2) evaluating response to a potential treatment with the use of miRNA mimics or inhibitors

Advances in imaging specific mediators of inflammatory bowel disease

Published: 21 August 2018Inflammatory bowel disease (IBD) is characterized by chronic remitting and relapsing inflammation of the lower gastrointestinal tract. The etiology underlying IBD remains unknown, but it is thought to involve a hypersensitive immune response to environmental antigens, including the microbiota. Diagnosis and monitoring of IBD is heavily reliant on endoscopy, which is invasive and does not provide information regarding specific mediators. This review describes recent developments in imaging of IBD with a focus on positron emission tomography (PET) and single-photon emission computed tomography (SPECT) of inflammatory mediators, and how these developments may be applied to the microbiota.Nicole Dmochowska, Hannah R. Wardill and Patrick A. Hughe

On the use of superparamagnetic hydroxyapatite nanoparticles as an agent for magnetic and nuclear in vivo imaging

The identification of alternative biocompatible magnetic NPs for advanced clinical application is becoming an important need due to raising concerns about iron accumulation in soft issues associated to the administration of superparamagnetic iron oxide nanoparticles (NPs). Here, we report on the performance of previously synthetized iron-doped hydroxyapatite (FeHA) NPs as contrast agent for magnetic resonance imaging (MRI). The MRI contrast abilities of FeHA and Endorem® (dextran coated iron oxide NPs) were assessed by 1H nuclear magnetic resonance relaxometry and their performance in healthy mice was monitored by a 7 Tesla scanner. FeHA applied a higher contrast enhancement, and had a longer endurance in the liver with respect to Endorem® at iron equality. Additionally, a proof of concept of FeHA use as scintigraphy imaging agent for positron emission tomography (PET) and single photon emission computed tomography (SPECT) was given labeling FeHA with 99mTc-MDP by a straightforward surface functionalization process. Scintigraphy/x-ray fused imaging and ex vivo studies confirmed its dominant accumulation in the liver, and secondarily in other organs of the mononuclear phagocyte system. FeHA efficiency as MRI-T2 and PET-SPECT imaging agent combined to its already reported intrinsic biocompatibility qualifies it as a promising material for innovative nanomedical applications. STATEMENT OF SIGNIFICANCE: The ability of iron-doped hydroxyapatite nanoaprticles (FeHA) to work in vivo as imaging agents for magnetic resonance (MR) and nuclear imaging is demonstrated. FeHA applied an higher MR contrast in the liver, spleen and kidneys of mice with respect to Endorem®. The successful radiolabeling of FeHA allowed for scintigraphy/X-ray and ex vivo biodistribution studies, confirming MR results and envisioning FeHA application for dual-imaging

Visualization and quantification of tumour biology for personalized radiotherapy

There are many types of cancer and there are significant differences between patients, between tumours, and even within a single tumour. These differences make cancer a difficult disease to cure and tend to result in different treatment outcomes. Functional imaging is a minimally invasive method of examining tumour biology in 3D. This dissertation used functional imaging techniques to classify the tumour and examine tumour sub-volumes. The absorption of a labelled drug, tumour circulation, tumour metabolism and tumour oxygen deficiency were measured and tested as markers to determine patient prognoses, to predict the treatment outcome and to adjust radiotherapy treatment plans