M. I. M. Prata

Bio: M. I. M. Prata is an academic researcher from University of Coimbra. The author has contributed to research in topics: Biodistribution & Asialoglycoprotein receptor. The author has an hindex of 11, co-authored 22 publications receiving 426 citations. Previous affiliations of M. I. M. Prata include University of Porto.

Lanthanide(III) complexes of DOTA-glycoconjugates: a potential new class of lectin-mediated medical imaging agents.

Abstract: Reference LCIB-ARTICLE-2004-002View record in Web of Science Record created on 2006-02-15, modified on 2017-05-12

First in vivo MRI assessment of a self‐assembled metallostar compound endowed with a remarkable high field relaxivity

Abstract: {Fe[Gd2bpy(DTTA)2(H2O)4]3}4- is a self-assembled, metallostar-structured potential MRI contrast agent, with six efficiently relaxing Gd3+ centers confined into a small mol. space. Its proton relaxivity is particularly remarkable at very high magnetic fields (r1 = 15.8 mM-1 s-1 at 200 MHz, 37°C, in H2O). Here we report the first in vivo MRI feasibility study, complemented with dynamic g scintigraphic imaging and biodistribution expts. using the 153Sm-enriched compd. Comparative MRI studies have been performed at 4.7 T in mice with the metallostar and the small mol. wt. contrast agent gadolinium(III)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate ([Gd(DOTA)(H2O)]- = GdDOTA). The metallostar was well tolerated by the animals at the concns. of 0.0500 (high dose) and 0.0125 (low dose) mmol Gd kg-1 body wt.; (BW). The signal enhancement in the inversion recovery fast low angle shot (IR FLASH) images after the high-dose metallostar injection was considerably higher than after GdDOTA injection (0.1 mmol Gd kg-1 BW), despite the higher dose of the latter. The high-dose metallostar injection resulted in a greater drop in the spin-lattice relaxation time (T1), as calcd. from the inversion recovery true fast imaging with steady-state precession (IR TrueFISP) data for various tissues, than the GdDOTA or the low dose metallostar injection. In summary, these studies have confirmed that the approx. four times higher relaxivity measured in vitro for the metallostar is retained under in vivo conditions. The pharmacokinetics of the metallostar was found to be similar to that of GdDOTA, involving fast renal clearance, a leakage to the extracellular space in the muscle tissue and no leakage to the brain. As expected on the basis of its moderate mol. wt., the metallostar does not function as a blood pool agent. The dynamic g scintigraphic studies performed in Wistar rats with the metallostar compd. having 153Sm enrichment also proved the renal elimination pathway. The biodistribution expts. are in full accordance with the MR and scintigraphic imaging. At 15 min post-injection the activity is primarily localized in the urine, while at 24 h post-injection almost all radioactivity is cleared from tissues and organs.

In vivo MRI assessment of a novel GdIII-based contrast agent designed for high magnetic field applications.

Abstract: Gd(3)L is a trinuclear Gd(3+) complex of intermediate size, designed for contrast agent applications in high field magnetic resonance imaging (H(12)L is based on a trimethylbenzene core bearing three methylene-diethylenetriamine- N,N,N'',N''-tetraacetate moieties). Thanks to its appropriate size, the presence of two inner sphere water molecules and a fast water exchange, Gd(3)L has remarkable proton relaxivities at high magnetic field (r(1) = 10.2 vs 3.0 mM(-1) s(-1) for GdDOTA at 9.4 T, 37 degrees C, in H(2)O). Here we report an in vivo MRI feasibility study, complemented with dynamic gamma scintigraphic imaging and biodistribution experiments using the (153)Sm-enriched analog. MRI experiments were performed at 9.4 T in mice with Gd(3)L and the commercial contrast agent gadolinium(III)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate (GdDOTA). Gd(3)L was well tolerated by the animals at the dose of 8 micromol Gd kg(-1) body weight. Dynamic contrast enhanced (DCE) images showed considerably higher signal enhancement in the kidney medulla and cortex after Gd(3)L injection than after GdDOTA injection at an identical dose. The relaxation rates, DeltaR(1), were calculated from the IR TrueFISP data. During the excretory phase, the DeltaR(1) for various tissues was similar for Gd(3)L and GdDOTA, when the latter was injected at a three-fold higher dose (24 vs 8 micromol Gd kg(-1) body weight). These results point to an approximately three times higher in vivo relaxivity (per Gd) for Gd(3)L relative to GdDOTA, thus the ratio of the relaxivities of the two compounds determined in vitro is retained under in vivo conditions. They also indicate that the two inner sphere water molecules per Gd in Gd(3)L are not substantially replaced by endogenous anions or other donor groups under physiological conditions. Gd(3)L has a pharmacokinetics typical of small, hydrophilic complexes, involving fast renal clearance and no retention in the blood pool. The dynamic gamma scintigraphic studies and the biodistribution experiments performed in Wistar rats with (153)Sm-enriched (*)Sm(3)L are also indicative of a fast elimination via the kidneys.

Lanthanide probes for bioresponsive imaging.

Abstract: The chemistry of the less familiar elements is a fascinating topic especially for the inorganic minded. The lanthanides, or rare earths, comprise the 5d block of the periodic table and represent a huge array of applications from catalysis to lasers, and of course, imaging agents.1 Recent advances in luminescence and magnetic resonance microscopy have, in part, been stimulated by extraordinary success in the development of new lanthanide probes. The unique properties of the lanthanides provide for a deep tool chest for the chemist, biologist and the imaging scientist to exploit, and that exploitation is in full swing. In this review we focus on two classes of lanthanide probes that are subsets of the larger area of metalloimaging: luminescent and magnetic lanthanides. In Section 2 we discuss the general design and photophysical properties of lanthanides and how these parameters are tuned to develop bioresponsive probes for optical imaging. In Section 3 we provide a brief description of how MR images are acquired and the how MRI contrast agents are engineered to respond to biological events of interest. These guiding principles have driven research that has produced a truly diverse number of new agents that are target specific and bioresponsive (or bioactivatable). While other imaging modalities utilize lanthanide-based probes, these topics are beyond the scope of this review. We direct the reader to explore some excellent reviews in the important areas of radiometals and multimodal imaging.2–5

Chemistry of MRI Contrast Agents: Current Challenges and New Frontiers

Abstract: Tens of millions of contrast-enhanced magnetic resonance imaging (MRI) exams are performed annually around the world. The contrast agents, which improve diagnostic accuracy, are almost exclusively small, hydrophilic gadolinium(III) based chelates. In recent years concerns have arisen surrounding the long-term safety of these compounds, and this has spurred research into alternatives. There has also been a push to develop new molecularly targeted contrast agents or agents that can sense pathological changes in the local environment. This comprehensive review describes the state of the art of clinically approved contrast agents, their mechanism of action, and factors influencing their safety. From there we describe different mechanisms of generating MR image contrast such as relaxation, chemical exchange saturation transfer, and direct detection and the types of molecules that are effective for these purposes. Next we describe efforts to make safer contrast agents either by increasing relaxivity, increasing resistance to metal ion release, or by moving to gadolinium(III)-free alternatives. Finally we survey approaches to make contrast agents more specific for pathology either by direct biochemical targeting or by the design of responsive or activatable contrast agents.

Coordinating Radiometals of Copper, Gallium, Indium, Yttrium and Zirconium for PET and SPECT Imaging of Disease

Abstract: Molecular imaging is the visualization, characterization and measurement of biological processes at the molecular and cellular levels in humans and other living systems. Molecular imaging agents are probes used to visualize, characterize and measure biological processes in living systems. These two definitions were put forth by the Sociey of Nuclear Medicine (SNM) in 2007 as a way to capture the interdisciplinary nature of this relatively new field. The emergence of molecular imaging as a scientific discipline is a result of advances in chemistry, biology, physics and engineering, and the application of imaging probes and technologies has reshaped the philosophy of drug discovery in the pharmaceutical sciences by providing more cost effective ways to evaluate the efficacy of a drug candidate and allowing pharmaceutical companies to reduce the time it takes to introduce new therapeutics to the marketplace. Finally the impact of molecular imaging on clinical medicine has been extensive since it allows a physician to diagnose a patient’s illness, prescribe treatment and monitor the efficacy of that treatment non-invasively. Single Photon Emission Computed Tomography (SPECT) and Positron Emission Tomography (PET) were the first molecular imaging modalities used clinically. SPECT requires the use of a contrast agent labeled with a gamma emitting radionuclide, which should have an ideal gamma energy of 100-250 keV. These gamma rays are recorded by the detectors of a dedicated gamma camera or SPECT instrument and after signal processing can be converted into an image indentifying the localization of the radiotracer. PET requires the injected radiopharmaceutical to be labeled with a positron emitting radionuclide. As the radionuclide decays it ejects a positron from its nucleus which travels a short distance before being annihilated with an electron to release two 511 keV gamma rays 180° apart that are detected by the PET scanner (Figure 1). After sufficient acquisition time the data are reconstructed using computer based algorithms to yield images of the radiotracer’s location within the organism. When compared to SPECT, PET has greater advantages with respect to sensitivity and resolution and has been gaining in clinical popularity, with the number of PET-based studies expected to reach 3.2 million by 2010.1 While SPECT and PET technology has been around for decades, its use remained limited because of the limited availability of relevant isotopes which had to be produced in nuclear reactors or particle accelerators. However, the introduction of the small biomedical cyclotron, the self-contained radionuclide generator and the dedicated small animal or clinical SPECT and PET scanners to hospitals and research facilities has increased the demand for SPECT and PET isotopes. Figure 1 Cartoon depicting the fundamental principle of Positron Emission Tomography (PET). As the targeting group interacts with the cell surface receptor, the positron emitting radio-metal decays by ejecting β+ particles from its nucleus. After traveling ... Traditional PET isotopes such as 18F, 15O, 13N and 11C have been developed for incorporation into small molecules, but due to their often lengthy radio-syntheses, short half-lives and rapid clearance, only early time points were available for imaging, leaving the investigation of biological processes, which occur over the duration of hours or days, difficult to explore. With the continuing development of biological targeting agents such as proteins, peptides, antibodies and nanoparticles, which demonstrate a range of biological half-lives, a need arose to produce new radionuclides with half-lives complementary with their biological properties. As a result, the production and radiochemistry of radiometals such as Zr, Y, In, Ga and Cu have been investigated as radionuclide labels for biomolecules since they have the potential to combine their favorable decay characteristics with the biological characteristics of the targeting molecule to become a useful radiopharmaceutical (Tables ​(Tables11 and ​and22).2 Table 1 Gamma- and Beta-Emitting Radiometals Table 2 Positron-Emitting Radiometals The number of papers published describing the production or use of these radiometals continues to expand rapidly, and in recognition of this fact, the authors have attempted to present a comprehensive review of this literature as it relates to the production, ligand development and radiopharmaceutical applications of radiometals (excluding 99mTc) since 1999. While numerous reviews have appeared describing certain aspects of the production, coordination chemistry or application of these radiometals,2-18 very few exhaustive reviews have been published.10,12 Additionally, this review has been written to be used as an individual resource or as a companion resource to the review written by Anderson and Welch in 1999.12 Together, they provide a literature survey spanning 50 years of scientific discovery. To accomplish this goal, this review has been organized into three sections: the first section discusses the coordination chemistry of the metal ions Zr, Y, In, Ga and Cu and their chelators in the context of radiopharmaceutical development; the second section describes the methods used to produce Zr, Y, In, Ga and Cu radioisotopes; and the final section describes the application of these radiometals in diagnostic imaging and radiotherapy.

Challenges for Molecular Magnetic Resonance Imaging

Abstract: 3.3. Magnetic Particle Imaging 3029 4. Challenges for CEST Agents 3029 4.1. Technical Issues 3029 4.2. Chemical Issues 3031 4.3. Biological Issues 3032 5. Challenges for Heteronuclear MR Imaging 3033 5.1. F-Based Probes 3033 6. Challenges for Hyperpolarized Probes 3034 6.1. Brute Force 3034 6.2. Optical Pumping and Spin Exchange 3035 6.3. Dynamic Nuclear Polarization (DNP) 3035 6.4. para-Hydrogen Induced Polarization (PHIP) 3037 6.5. Use of Gd Contrast Agents with Hyperpolarized Substances 3038

Macromolecules, Dendrimers, and Nanomaterials in Magnetic Resonance Imaging: The Interplay between Size, Function, and Pharmacokinetics

Abstract: Magnetism in medicine has had a long and interesting history In the 10 th century AD, Egyptian physician and philosopher Avicenna prescribed a grain of magnetite dissolved in milk for the accidental swallowing of rust reasoning that magnetite would render the poisonous iron inert by attracting it and accelerating its excretion through the intestine1 A thousand years later on July 3, 1977, “Indomitable”, the little machine that could, labored for five hours to produce one image, an event that used magnetism to change the landscape of modern medicine 2 Looking at the homemade superconducting magnet constructed from 30 miles of niobiumtitanium wire that now resides in its rightful place at the Smithsonian Institution, it is incredible to comprehend how in a mere 30 years magnetic resonance imaging (MRI) has gone from its crude, almost ugly, human scan to where physicians can now regularly order MRIs off their menu of diagnostic tools because of its exquisite anatomical resolution, routinely down to 05 to 1 mm When the field was first reviewed in this journal in 1987, 3 only 39 papers were found in Medline with keywords “gado-“ and “MRI” 4 Today, this same search on PubMed pulls out over 250,000 records, of which a significant component has been development of MR contrast agents The human body is essentially a super-sized water bottle, with about two-thirds of its weight consisting of water Water's hydrogen atoms are able to act as microscopic compass needles that stand “at attention” when placed in a strong magnetic field When submitted to pulses of radio waves, their magnetic alignment is disrupted and the differences in how they relax to the previous state are used to generate images Contrast agents can act to catalyze the process of the return to the ground relaxed state Now commonplace in the clinic, paramagnetic or superparamagnetic metal ions are administered in 40–50% of the 7–10 million MR examinations per year 5 These image-enhancing contrast agents add significant morphological and functional information to unenhanced MR images, allowing for enhanced tissue contrast, characterization of lesions, and evaluation of perfusion and flow-related abnormalities In this review, we will introduce small molecule agents, but focus primarily on macromolecular MR contrast agents, particularly those containing gadolinium (Gd 3+ ) that are assembled or based in part on these same small molecules A brief discussion on iron oxide and manganese (Mn 2+ ) agents is also provided