Cristina Rodriguez-Rodriguez

Cristina Rodriguez-Rodriguez
University of British Columbia - Vancouver | UBC · Department of Physics and Astronomy | Faculty of Pharmaceutical Sciences

PhD in Chemistry

About

57
Publications
7,292
Reads
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1,035
Citations
Introduction
Cristina Rodriguez received her Ph.D. degree in Chemistry at the University Autonomous of Barcelona in Spain. In 2010, she joined Chris Orvig's lab at the University of British Columbia (UBC) as a postdoctoral fellow. In 2014, Cristina joined the UBC In vivo Imaging lab as a Research Associate | Lab Manager where she is the responsible for the coordination and performance of SPECT/PET/CT Preclinical Imaging Projects (www.invivoimaging.ca)
Additional affiliations
October 2014 - December 2017
University of British Columbia - Vancouver
Position
  • Laboratory Manager | Research Associate
July 2010 - September 2014
University of British Columbia - Vancouver
Position
  • PostDoc Position

Publications

Publications (57)
Article
With the growing interest in developing silver-based antimicrobials, there is a need to better understand the behavior of silver within biological systems. To address this, we showed that single-photon emission computed tomography (SPECT) is a suitable method to noninvasively image 111Ag-labeled compounds in mice. Formed by neutron irradiation of p...
Article
Human insulin (HI) has fascinating metal-facilitated self-assembly properties that are essential for its biological function. HI has a natural Zn²⁺ binding site and we have previously shown that covalently attached abiotic ligands (e.g., bipyridine, terpyridine) can lead to the formation of nanosized oligomeric structures through the coordination o...
Article
Radiolabeling of a drug with radioactive iodine is a good method to determine its pharmacokinetics and biodistribution in vivo that only minimally alters its physicochemical properties. With dual labeling, using the two radioactive iodine isotopes 123I and 125I, two different drugs can be evaluated at the same time, or one can follow both a drug an...
Article
Albumin is widely used in pharmaceutical applications to alter the pharmacokinetic profile, improve efficacy, or decrease the toxicity of active compounds. Various drug delivery systems using albumin have been reported, including microparticles. Macroaggregated albumin (MAA) is one of the more common forms of albumin microparticles, which is predom...
Article
Following murine injection, the ultrastructural loci of nanoparticles (NPs) containing lutetium-177 (Lu-177) conjugated to an anti-thrombomodulin antibody (mAb-201b) were determined. The results confirmed prior work localizing NPs using Single Photon Emission Computed Tomography (SPECT) scans. The in vivo pharmacokinetics of these NPs were also ide...
Article
The validation of metal-phenolic nanoparticles (MPNs) in preclinical imaging studies represents a growing field of interest due to their versatility in forming predesigned structures with unique properties. Before MPNs can be used in medicine, their pharmacokinetics must be optimized so that accumulation in nontargeted organs is prevented and toxic...
Article
Pulmonary delivery of small interfering RNA (siRNA)-based drugs is promising in treating severe lung disorders characterized by the upregulated expression of disease-causing genes. Previous studies have shown that the sustained siRNA release in vitro can be achieved from polymeric matrix nanoparticles based on poly(lactide-co-glycolide) (PLGA) load...
Article
Full-text available
Background The discovery and development of new medicines requires high-throughput screening of possible therapeutics in a specific model of the disease. Infrared thermal imaging (IRT) is a modern assessment method with extensive clinical and preclinical applications. Employing IRT in longitudinal preclinical setting to monitor arthritis onset, dis...
Article
Controlled self-assembly of peptide- and protein-based pharmaceuticals is of central importance for their mode of action and tuning of their properties. Peptide YY 3-36 (PYY 3-36 ) is a 36 amino acid peptide hormone that reduces food intake when peripherally administered. Herein, we describe the synthesis of a PYY 3-36 analogue functionalized with...
Article
Targeted alpha‐therapy (TAT) has great potential for treating a broad range of late stage cancers by delivering a focused and lethal radiation dose to tumors. Actinium‐225 ( 225 Ac) is an emerging alpha emitter suitable for TAT, however the availability of chelators for Ac remains limited to a small number of examples (DOTA and macropa). Herein we...
Article
Local as well as systemic therapy is often used to treat bacterial lung infections. Delivery of antibiotics to the vascular side of infected lung tissue by using lung-targeting microspheres (MS) is a good alternative to conventional administration routes, allowing for localized high levels of antibiotics. This delivery route can also complement inh...
Article
Pulmonary formulations have been attracting much attention because of their direct effects on respiratory diseases, but also their non-invasive administration for the treatment of systemic diseases. When developing such formulations, they are typically first investigated in mice. As there are various pulmonary administration methods, the researcher...
Article
A rigid chiral acyclic chelator H2CHXhox was synthesized and evaluated for Ga3+-based radiopharmaceutical applications; it was compared to the previously reported hexadentate H2hox to determine the effect of a backbone reinforced from adding a chiral 1S,2S-trans-cyclohexane on metal complex stability, kinetic inertness, and in vivo pharmacokinetics...
Article
Using lipid-based drug delivery systems (LbDDS) is an efficient strategy to enhance the low oral bioavailability of poorly water-soluble drugs. Here the oral absorption of fenofibrate (FF) from LbDDS in rats was investigated in pharmacokinetic, in vitro lipolysis, and SPECT/CT in vivo imaging studies. The investigated formulations were soybean oil...
Article
Full-text available
Background: Actinium-225 (225Ac, t1/2 = 9.9 d) is a promising candidate radionuclide for use in targeted alpha therapy (TAT), though the currently limited global supply has hindered the development of a suitable Ac-chelating ligand and 225Ac-radiopharmaceuticals towards the clinic. We at TRIUMF have leveraged our Isotope Separation On-Line (ISOL)...
Article
Full-text available
A common form of treatment for patients with hepatocellular carcinoma (HCC) is transarterial radioembolization (TARE) with non-degradable glass or resin microspheres (MS) labeled with 90Y (90Y-MS). To further simplify the dosimetry calculations in the clinical setting, to have more control over the particle size and to change the permanent emboliza...
Article
Full-text available
Pulmonary tuberculosis (TB), which is caused by Mycobacterium tuberculosis (Mtb), remains a global pandemic, despite the widespread use of the parenteral live attenuated Bacillus Calmette–Guérin (BCG) vaccine during the past decades. Mucosal administration of next generation TB vaccines has great potential, but developing a safe and efficacious muc...
Article
Dual-isotope (DI) studies offer a number of advantages in pre-clinical imaging. These include: reducing study times when compared with sequential scans, reducing the number of animals required for any given study, and most importantly, producing images perfectly registered in space and time that provide simultaneous information about two distinct b...
Article
Full-text available
Targeted radiotherapies maximize cytotoxicity to cancer cells. In this work, we describe the synthesis, characterization, and biodistribution of antibody conjugated gold-coated lanthanide phosphate nanoparticles containing ¹⁷⁷Lu. [¹⁷⁷Lu]Lu0.5Gd0.5(PO4)@Au@PEG800@Ab nanoparticles combine the radiation resistance of crystalline lanthanide phosphate f...
Article
The development of alpha-emitting radiopharmaceuticals using <sup>211</sup>At requires quantitative determination of the time-dependent nature of the <sup>211</sup>At biodistribution. However, imaging-based methods for acquiring this information with <sup>211</sup>At have not found wide-spread use because of its low abundance of decay emissions sui...
Article
H2macropa, an 18-membered macrocycle, was investigated for 225Ac chelation in targeted alpha therapy (TAT). Radiolabeling studies showed that macropa, at submicromolar concentration, complexed all 225Ac (26 kBq) in 5 min at RT. [225Ac(macropa)]+ remained intact over 7-8 days when challenged with either excess La3+ ions or human serum, and did not a...
Article
H2macropa, an 18-membered macrocycle, was investigated for 225Ac chelation in targeted alpha therapy (TAT). Radiolabeling studies showed that macropa, at submicromolar concentration, complexed all 225Ac (26 kBq) in 5 min at RT. [225Ac(macropa)]+ remained intact over 7-8 days when challenged with either excess La3+ ions or human serum, and did not a...
Article
The main applications of 188 Re in radionuclide therapies include trans-arterial liver radioembolization and palliation of painful bone-metastases. In order to optimize 188 Re therapies, the accurate determination of radiation dose delivered to tumors and organs at risk is required. Single photon emission computed tomography (SPECT) can be used to...
Article
Zirconium-89 (89Zr) is an ideal radiometal isotope for antibody-based positron emission tomography (immunoPET) as its physical half-life (3.27 days) is a good match with the biological half-life of larger molecular weight targeting molecules, such as antibodies (3-4 days), and its positron emission (BR = 100% EC/[small beta]+, E[small beta]+,avg =...
Article
Effective use of the ²²⁵Ac decay chain in targeted internal radioimmunotherapy requires the retention of both ²²⁵Ac and progeny isotopes at the target site. Imaging-based pharmacokinetic tests of these pharmaceuticals must therefore separately yet simultaneously image multiple isotopes that may not be colocalized despite being part of the same deca...
Article
Purpose: The goal of this study was to investigate the performance of a pre-clinical SPECT/PET/CT system for (188)Re imaging. Methods: Phantom experiments were performed aiming to assess the characteristics of two multi-pinhole collimators: ultra-high resolution collimator (UHRC) and high-energy ultra high resolution collimator (HE-URHC) for ima...
Article
Full-text available
Purpose: In the nuclear medicine department, the activity of radiopharmaceuticals is measured using dose calibrators (DCs) prior to patient injection. The DC consists of an ionization chamber that measures current generated by ionizing radiation (emitted from the radiotracer). In order to obtain an activity reading, the current is converted into un...
Article
We have previously shown the improved acetylcholinesterase inhibitory activity of a model hydroxypyridinone compound transforming the hydroxyl group on the main ring into an N,N-dimethylcarbamate group; in the course of that study we developed a computational model to screen compounds for enzymatic activity. Herein we report development of second g...
Article
Finding a cure for Alzheimer's disease is an urgent goal. Multifunctional metal binders are used to elucidate its pathological features and investigated as potential therapeutics. The use of physicochemical and TD-DFT calculations constituted successful strategy in the design of 1-(4-(benzo[d]oxazol-2-yl)phenyl)-3-hydroxy-2-methylpyridin-4(1H)-one...
Article
Alzheimer’s disease is a neurological disease of confusing causation with no cure or prevention available. The definitive diagnosis is made postmortem, in part through the presence of amyloid-beta plaques in the brain tissue, which can be done with the small molecule thioflavin-T (ThT). Plaques are also found to contain elevated amounts of metal io...
Conference Paper
The present contribution analyzes the binding of ThT and neutral ThT derivatives to a β-sheet model by means of quantum chemical calculations. In addition, we study the properties of four molecules: (2-(2-hydroxyphenyl)benzoxazole (HBX), 2-(2-hydroxyphenyl)benzothiazole (HBT) and their respective iodinated compounds, HBXI and HBTI, in binding to am...
Conference Paper
Metal cations such as Cu 2+ have been shown to induce amyloid aggregation and formation of reactive oxygen species. Elucidation of the structural features of Cu 2+ − A β is thus, essential to understand their role in the aggregation of Aβ, formation of ROS and to rationally design new chelators with potential therapeutic applications. Pre...
Article
Full-text available
Metal ions have been implicated in several neurodegenerative diseases, including Alzheimer's disease, as their dyshomeostasis may lead to production of reactive oxygen species as well as increased toxicity of amyloid protein aggregates. In this work, we present design and synthesis of three novel multifunctional hydroxypyridinone ligands, , , and ,...
Article
Thioflavin-T (ThT) is one of the most widely used dyes for staining and identifying amyloid fibrils, which share a common parallel in register b-sheet structure. Unfortunately, ThT is a charged molecule, which limits its ability to cross the blood brain barrier and its use as an efficient dye for in vivo detection of amyloid fibrils. For this reaso...
Article
Alzheimer's disease (AD) is a devastating neurodegenerative disease that affects millions of people worldwide. With no prevention or cure available, this progressive disease has a significant impact on society - dementia patients and their caretakers, healthcare systems, and the economy. Previously, we have reported initial developments of multifun...
Article
The deleterious role of metal ions in Alzheimer’s disease has inspired the study of various metal chelators. We previously showed the synthesis and in vitro activity of several bidentate hydroxypyridinone compounds, including 3-hydroxy-2-methyl-1-phenyl-4(1H)-pyridinone (1), 1-(4-aminophenyl)-3-hydroxy-2-methyl-4(1H)-pyridinone (2), and 1-(2-benzot...
Article
Metal-ion homeostasis in the brain is critical for many physiological functions, particularly in the central nervous system where metals are essential in complex signaling pathways. Most common neurological diseases such as Alzheimer's (AD), Parkinson's (PD) and prion diseases, despite having distinct etiological bases, share similarities associate...
Article
Full-text available
Molecules designed to sequester, redistribute and/or remove metal ions are attractive therapeutic agents in neurodegenerative diseases such as Alzheimer's disease. The multifactorial nature of the condition and the generally poor target specificity associated with metal ion-binding therapy has led to the development of multifunctional 3-hydroxy-4-(...
Article
Full-text available
The development of new strategies to find commercial molecules with promising biochemical features is a main target in the field of biomedicine chemistry. In this work we present an in silico-based protocol that allows identifying commercial compounds with suitable metal coordinating and pharmacokinetic properties to act as metal-ion chelators in m...
Article
Combining X-ray data on thioflavin-T and theoretical calculations on its binding to a peptide model for Abeta(1-42) fibrils gives evidence of main stabilizing interactions, which influence the dihedral angle between the two moieties of thioflavin-T and thereby its fluorescence properties; these results shed new light on possible strategies for the...
Article
We describe an experiment in which the UV–vis spectrum of 8-hydroxyquinoline-5-sulfonic acid (8HQS) is measured as a function of pH. This experiment introduces students to the chemometric treatments of evolving signals by means of multivariate curve resolution-alternating least squares (MCR-ALS). This is a well established decomposition method to o...

Projects

Projects (2)
Project
In vivo non-invasive imaging methods, such as single photon emission computed tomography (SPECT) and positron emission tomography (PET), allow the direct quantification of functional processes and metabolic rates in animal models using target- or disease- specific biomarkers. In vivo Imaging can replace time-consuming and less reliable ex vivo and in vitro methods in many areas of biomedical science. It accelerates drug and radiopharmaceuticals allowing an easy translation of results from the laboratory bench to the clinics. A multidisciplinary team of highly motivated and skilled physicists, chemists, , and pharmacists form the In Vivo Imaging Lab at University of British Columbia and run the state-of-the-art PET/SPECT/CT small animal preclinical scanner. We invite you to visit our webpage www.invivoimaging.ca to learn about our research and the fascinating options that in vivo preclinical imaging offers.