
Rafael T. M. de Rosales (Torres Martin de Rosales)King's College London | KCL · School of Biomedical Engineering & Imaging Sciences
Rafael T. M. de Rosales (Torres Martin de Rosales)
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94
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Introduction
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January 2009 - December 2012
Publications
Publications (94)
The clinical value of current and future nanomedicines can be improved by introducing patient selection strategies based on noninvasive sensitive whole-body imaging techniques such as positron emission tomography (PET). Thus, a broad method to radiolabel and track preformed nanomedicines such as liposomal drugs with PET radionuclides will have a wi...
The efficient delivery of nanomaterials to specific targets for in vivo biomedical imaging is hindered by rapid sequestration by the reticuloendothelial system (RES) and consequent short circulation times. In order to overcome these two problems, we have prepared a new stealth PEG polymer conjugate containing a terminal 1,1-bisphosphonate (BP) grou...
A novel bifunctional chelator combines a dithiocarbamate group for binding the positron-emitter 64Cu (red spheres) for PET imaging and a bisphosphonate group (green ellipsoids) for strong binding to several inorganic materials, such as MRI contrast agents based on superparamagnetic iron oxide nanoparticles and rare-earth metal oxides. The dual PET-...
Inhalation of biopersistent nanoplastics may have adverse effects on lung health. By varying the acetate content of poly(vinyl acetate‐co‐alcohol) (PVAc), model nanoplastics with different surface hydrophobicity can be produced to study the effects of nanoplastic hydrophobicity in the lung. PVAc nanoplastics with a high hydrophobicity, administered...
Prussian blue is known for its high affinity for thallium and other univalent metal cations and has been used as a treatment for radiocaesium and thallium/radiothallium poisoning. While Prussian blue nanoparticles (PBNPs) show potential for binding radioactive thallium for further use in nuclear medicine applications, the inclusion mechanism remain...
Pretargeted PET imaging using bioorthogonal chemistry is a leading strategy for the tracking of long-circulating agents such as antibodies and nanoparticle-drug delivery systems with short-lived isotopes. Here, we report the...
Pretargeted PET imaging using bioorthogonal chemistry is a leading strategy for the tracking of long-circulating agents such as antibodies and nanoparticle-drug delivery systems with short-lived isotopes. Here, we report the synthesis, characterisation and in vitro/vivo evaluation of a new 68Ga-based radiotracer [68Ga]Ga-THP-Tetrazine ([68Ga]Ga-THP...
Positron emission particle tracking (PEPT) enables 3D localization and tracking of single positron-emitting radiolabelled particles with high spatiotemporal resolution. The translation of PEPT to the biomedical imaging field has been limited due to the lack of methods to radiolabel biocompatible particles with sufficient specific activity and proto...
Encapsulation of Doxorubicin (Dox), a potent cytotoxic agent and immunogenic cell death inducer, in pegylated (Stealth) liposomes, is well known to have major pharmacologic advantages over treatment with free Dox. Reformulation of alendronate (Ald), a potent amino-bisphosphonate, by encapsulation in pegylated liposomes, results in significant immun...
Background
The ability of CD8+ T cells to protect against infection and malignant transformation diminishes with age. Novel means to assess cellular functional deficits in vivo are being made available such as total-body positron emission tomography (PET) and radiotracers with long half-lives. Here, we determined radiolabeled human CD8+ T cells iso...
Radiolabelled bisphosphonates (BPs) and [¹⁸F]NaF (¹⁸F-fluoride) are the two types of radiotracers available to image calcium mineral (e.g. bone), yet only [¹⁸F]NaF has been widely explored for the non-invasive molecular imaging of extraosseous calcification (EC) using positron emission tomography (PET) imaging. These two radiotracers bind calcium m...
Direct delivery to the lung via inhalation is arguably one of the most logical approaches to treat lung cancer using drugs. However, despite significant efforts and investment in this area, this strategy has not progressed in clinical trials. Imaging drug delivery is a powerful tool to understand and develop novel drug delivery strategies. In this...
Radiolabelled bisphosphonates (BPs) and [ ¹⁸ F]NaF ( ¹⁸ F-fluoride) are the two types of radiotracers available to image calcium mineral in vivo (e.g. bone), yet only [ ¹⁸ F]NaF has been widely explored for the non-invasive molecular imaging of extraosseous calcification (EC) using the highly sensitive nuclear imaging technique positron emission to...
Background
Manganese porphyrins have several therapeutic/imaging applications, including their use as radioprotectants (in clinical trials) and as paramagnetic MRI contrast agents. The affinity of porphyrins for lipid bilayers also makes them candidates for cell/liposome labelling. We hypothesised that metalation with the positron emission tomograp...
The arrival of cell-based therapies is a revolution in medicine. However, its safe clinical application in a rational manner depends on reliable, clinically applicable methods for determining the fate and trafficking of therapeutic cells in vivo using medical imaging techniques─known as in vivo cell tracking. Radionuclide imaging using single photo...
Manganese porphyrins have several therapeutic/imaging applications, including their use as radioprotectants (in clinical trials) and as paramagnetic MRI contrast agents. The affinity of porphyrins for lipid bilayers also makes them candidates for cell/liposome labelling. We hypothesised that metalation with the positron emission tomography (PET) ra...
Exosomes or small extracellular vesicles (sEVs) are increasingly gaining attention for their potential as drug delivery systems and biomarkers of disease. Therefore, it is important to understand their in vivo biodistribution using imaging techniques that allow tracking over time and at the whole-body level. Positron emission tomography (PET) allow...
Despite its role in cancer surveillance, adoptive immunotherapy using γδ T cells has achieved limited efficacy. To enhance trafficking to bone marrow, circulating Vγ9Vδ2 T cells are expanded in serum-free medium containing TGF-β1 and IL-2 (γδ[T2] cells) or medium containing IL-2 alone (γδ[2] cells, as the control). Unexpectedly, the yield and viabi...
Manganese porphyrins have several therapeutic/imaging applications; including their use as radioprotectants (in clinical trials), and as paramagnetic MRI contrast agents. The affinity of porphyrins for lipid bilayers also makes them candidates for cell/liposome labelling. We hypothesised that metalation with the positron emission tomography (PET) r...
Hexadentate tris(3,4-hydroxypyridinone) ligands (THP) complex Fe3+ at very low iron concentrations and their high affinities for oxophilic trivalent metal ions have led to their development for new applications as bifunctional chelators for the radiometal gallium-68 (68Ga). THP-peptide bioconjugates rapidly and quantitatively complex 68Ga at room t...
Magnetic hyperthermia (MH) harnesses the heat‐releasing properties of superparamagnetic iron oxide nanoparticles (SPIONs) and has potential to stimulate immune activation in the tumor microenvironment whilst sparing surrounding normal tissues. To assess feasibility of localized MH in vivo, SPIONs are injected intratumorally and their fate tracked b...
Extracellular vesicles (EVs) such as exosomes and microvesicles have gained recent attention as potential biomarkers of disease as well as nanomedicinal tools, but their behaviour in vivo remains mostly unexplored. In order to gain knowledge of their in vivo biodistribution it is important to develop imaging tools that allow us to track EVs over ti...
Nanomaterials offer unique physical, chemical and biological properties of interest for medical imaging and therapy. Over the last two decades, there has been an increasing effort to translate nanomaterial-based medicinal products (so-called nanomedicines) into clinical practice and, although multiple nanoparticle-based formulations are clinically...
Background:
Advances in immunology and cell-based therapies are creating a need to track individual cell types, such as immune cells (neutrophils, eosinophils, chimeric antigen receptor (CAR) T cells, etc.) and stem cells. As the fate of administered cells remains largely unknown, nuclear imaging could determine the migration and survival of cells...
Calcium minerals such as hydroxyapatite (HAp) can be detected non-invasively in vivo using nuclear imaging agents such as [18F]NaF (available from cyclotrons), for positron emission tomography (PET) and 99mTc-radiolabelled bisphosphonates (BP; available from 99mTc generators for single photon emission computed tomography (SPECT) or scintigraphy). T...
89Zr]Zr(oxinate)4 allows direct radiolabelling of exosomes/small extracellular vesicles (sEVs) and in vivo PET-CT imaging
Chimeric antigen receptor T-cell therapy (CAR-T) has been rolled out as a new treatment for haematological malignancies. For solid tumour treatment, CAR-T has been disappointing so far. Challenges include the quantification of CAR-T trafficking into tumours, expansion and retention in tumours, activity at target sites, toxicities and long-term CAR-...
The encapsulation of Glucocorticoids (GCs) into long-circulating liposomes (LCLs) is a proven strategy to reduce the side effects of glucocorticoids and improve the treatment of inflammatory diseases, such as rheumatoid arthritis (RA). With the aim of supporting the development of GC-loaded LCLs, and potentially predict patient response to therapy...
Sentinel lymph node biopsy (SLNB) is commonly performed in cancers that metastasise via the lymphatic system. It involves excision and histology of sentinel lymph nodes (SLNs) and presents two main challenges: (i) sensitive whole-body localisation of SLNs, and (ii) lack of pre-operative knowledge of their metastatic status, resulting in a high numb...
The integration of nuclear imaging with nanomedicine is a powerful tool for efficient development and clinical translation of liposomal drug delivery systems. Furthermore, it may allow highly efficient imaging-guided personalised treatments. In this article, we critically review methods available for radiolabelling liposomes. We discuss the influen...
Gammadelta T (γδ-T) cells are strong candidates for adoptive immunotherapy in oncology due to their cytotoxicity, ease of expansion, and favorable safety profile. The development of γδ-T cell therapies would benefit from non-invasive cell-tracking methods and increased targeting to tumor sites. Here we report the use of [⁸⁹Zr]Zr(oxinate)4 to track...
Imaging plays a key role in the preclinical evaluation of nanomedicine-based drug delivery systems and it has provided important insights into their mechanism of action and therapeutic effect. Its role in supporting the clinical development of nanomedicine products, however, has been less explored. In this review, we summarize clinical studies in w...
Direct in vivo monitoring of bioconstructs using noninvasive imaging modalities such as magnetic resonance imaging (MRI) or computed tomography (CT) is not possible for many materials. Calcium phosphate–based composites (CPCs) that are applicable to bone regeneration are an example where the materials have poor MRI and CT contrast; hence, they are...
The ionophore 8-hydroxyquinoline (oxine) has been used to radiolabel cells and liposomal medicines with ¹¹¹In and, more recently, ⁸⁹Zr, for medical nuclear imaging applications. Oxine has also shown promising ionophore activity for the positron-emitting radionuclide ⁵²Mn that should allow imaging of labelled cells and nanomedicines for long periods...
The magnetic properties and safety of dextran-coated superparamagnetic iron oxide nanoparticles (SPIONs) have facilitated their clinical use as MRI contrast agents and stimulated research on applications for SPIONs in particle imaging and magnetic hyperthermia. The wider clinical potential of SPIONs, however, has been limited by their rapid removal...
Molecular imaging of drugs or drug carriers is a valuable tool that can provide important information on spatiotemporal distribution of drugs, allowing improved drug distribution at target sites. Chemically labelled drugs can be used to both diagnose and treat diseases. This book introduces the topic of image guided drug delivery and covers the lat...
We report a reproducible single-step, microwave-assisted approach for the preparation of multifunctional
magnetic nanocomposites comprising superparamagnetic iron oxide (Fe3O4) cores,
a polyelectrolyte stabilizer and an organic dye with no requirement for post-processing. The stabilisers
poly(sodium 4-styrenesulfonate (PSSS) and sodium polyphosphat...
Lipid nanocapsules (LNCs) are semi-rigid spherical capsules with a triglyceride core that present a promising formulation option for the pulmonary delivery of drugs with poor aqueous solubility. Whilst the biodistribution of LNCs of different size has been studied following intravenous administration, the fate of LNCs following pulmonary delivery h...
19F-magnetic resonance imaging (MRI) is a promising technique that may allow us to measure the concentration of exogenous fluorinated imaging probes quantitatively in vivo. Here, we describe the synthesis and characterisation of a novel geminal bisphosphonate (19F-BP) that contains chemically-equivalent fluorine atoms that show a single and narrow...
Carbon nanotubes (CNTs) have been advocated as promising nanocarriers in the biomedical field. Their high surface area and needle-like shape make these systems especially attractive for diagnostic and therapeutic applications. Biocompatibility, cell internalization, biodistribution, and pharmacokinetic profile have all been reported to be length de...
Nuclear magnetic relaxation dispersion (NMRD) profiles are essential tools to evaluate the efficiency and investigate the properties of magnetic compounds used as contrast agents for magnetic resonance imaging (MRI), namely gadolinium chelates and superparamagnetic iron oxide particles. These curves represent the evolution of proton relaxation rate...
The phase transfer of quantum dots to water is an important aspect of preparing nanomaterials that are suitable for biological applications, and although numerous reports describe ligand exchange, very few describe efficient ligand encapsulation techniques. In this report, we not only report a new method of phase transferring QDs using a novel amph...
PET-MR imaging is an exciting field of research for imaging chemists that allows for innovative approaches such as the use of cocktails of agents or bimodal contrast. In this review, we provide an overview of some of the work in the in preclinical and clinical PET-MR imaging to date, and discuss limitations in the design and applications of these m...
The development of medical imaging is a highly multidisciplinary endeavor requiring the close cooperation of clinicians, physicists, engineers, biologists, and chemists to identify capabilities, conceive challenges and solutions and apply them in the clinic. The chemistry described in this chapter illustrates how synergistic advances in these areas...
Multi-modal nanoparticulate materials are described, offering magnetic, radionuclide and fluorescent imaging capabilities to exploit the complementary advantages of magnetic resonance imaging (MRI), positron emission tomography/single-photon emission commuted tomography (PET/SPECT) and optical imaging. They comprise Fe3O4@NaYF4 core/shell nanoparti...
We report on a versatile and time-efficient method to fabricate calcium phosphate (CaP) microcapsules by utilizing oil-in-water emulsion droplets stabilized with synthetic branched copolymer (BCP) as templates. The BCP was designed to provide a suitable architecture and functionality to produce stable emulsion droplets, and to permit the mineraliza...
The development of clinically acceptable albumin-based nanoparticle formulations for use in pulmonary drug delivery has been hindered by concerns about the toxicity of nanomaterials in the lungs combined with a lack of information on albumin nanoparticle clearance kinetics and biodistribution. In this study, the in vivo biocompatibility of albumin...
Rationale:
Matrix vesicles (MVs), secreted by vascular smooth muscle cells (VSMCs), form the first nidus for mineralization and fetuin-A, a potent circulating inhibitor of calcification, is specifically loaded into MVs. However, the processes of fetuin-A intracellular trafficking and MV biogenesis are poorly understood.
Objective:
The objective...
The first 99mTc and 188Re radiopharmaceuticals containing two pendant bisphosphonate groups has been synthesised, based on the mononuclear M(V) nitride core with two dithiocarbamate ligands each with a pendant bisphosphonate. The structural identity of the 99Tc and stable rhenium analogues as uncharged, mononuclear nitridobis(dithiocarbamate) compl...
Magnetic nanoparticles (NPs) MnFe2O4 and Fe3O4 were stabilised by depositing an Al(OH)3 layer via a
hydrolysis process. The particles displayed excellent colloidal stability in water and a high affinity to
[18F]-fluoride and bisphosphonate groups. A high radiolabeling efficiency, 97% for 18F-fluoride and 100%
for 64Cu-bisphosphonate conjugate, was...
The introduction to the clinic of positron emission tomography-magnetic resonance imaging scanners opens up the possibility to evaluate the real potential of bimodal imaging agents. In this mini-review, the limitations in the design and applications of these materials are summarised and the unique properties that may result in real clinical applica...