Theranostics Using MCM-41-Based Mesoporous Silica Nanoparticles: Integrating Magnetic Resonance Imaging and Novel Chemotherapy for Breast Cancer Treatment.

Advanced breast cancer remains a significant oncological challenge, requiring new approaches to improve clinical outcomes. This study investigated an innovative theranostic agent using the MCM-41-NH2-DTPA-Gd3⁺-MIH nanomaterial, which combined MRI imaging for detection and a novel chemotherapy agent (MIH 2.4Bl) for treatment. The nanomaterial was based on the mesoporous silica type, MCM-41, and was optimized for drug delivery via functionalization with amine groups and conjugation with DTPA and complexation with Gd3+. MRI sensitivity was enhanced by using gadolinium-based contrast agents, which are crucial in identifying early neoplastic lesions. MIH 2.4Bl, with its unique mesoionic structure, allows effective interactions with biomolecules that facilitate its intracellular antitumoral activity. Physicochemical characterization confirmed the nanomaterial synthesis and effective drug incorporation, with 15% of MIH 2.4Bl being adsorbed. Drug release assays indicated that approximately 50% was released within 8 h. MRI phantom studies demonstrated the superior imaging capability of the nanomaterial, with a relaxivity significantly higher than that of the commercial agent Magnevist. In vitro cellular cytotoxicity assays, the effectiveness of the nanomaterial in killing MDA-MB-231 breast cancer cells was demonstrated at an EC50 concentration of 12.6 mg/mL compared to an EC50 concentration of 68.9 mg/mL in normal human mammary epithelial cells (HMECs). In vivo, MRI evaluation in a 4T1 syngeneic mouse model confirmed its efficacy as a contrast agent. This study highlighted the theranostic capabilities of MCM-41-NH2-DTPA-Gd3⁺-MIH and its potential to enhance breast cancer management.

Electrical bioimpedance analysis and comparison in biological tissues through crystalloid solutions implementation.

Electrical bioimpedance is a non-invasive and radiation-free technique that was proposed to be used in different clinical areas, however, its practical use is limited due to its low capacity to discriminate between tissues. In order to overcome this limitation, our research group proposes to incorporate the contrast media into the electrical bioimpedance procedure. The main objective of the present study was to assess the crystalloid solutions as a possible contrast media to discriminate between different tissue types in the bioimpedance technique. Two medical-grade crystalloid solutions (Hartmann and NaCl 0.9%) were injected into three biological ex vivo models: kidney, liver, and brain. BIOPAC system was used to acquire bioimpedance data before and after the injections. The data was adjusted to the Debye electrical model. The analysis of measured values showed substantial bioimpedance disparities in tissues subjected to isotonic solutions. The NaCl solution exhibited more pronounced changes in electrical parameters compared to the Hartmann solution. Similarly, NaCl solution displayed superior discriminatory capabilities among tissues, with variations of 465%, 157%, and 206%. Distinct spectral modifications were identified, with tissues demonstrating unique responses at each frequency of analysis relative to untreated tissue. Variations in bandwidth alterations were discernible among tissues, providing clear distinctions. In conclusion, the research showed that the crystalloid solution exhibited greater sensitivity and superior tissue contrast at specific frequencies. This study's findings underscore the feasibility of implementing crystalloid solutions to enhance tissue discrimination, similar to the effects of contrast agents.

Role of contrast agent in evaluation of periprostatic invasion in prostate cancer.

Objectives: Our study aims to demonstrate the detection of invasion by biparametric prostate MRI (bpMRI). Materials and methods: The cases whose histopathological diagnosis was prostate cancer (PCa) and whose mpMRI report was reported as PIRADS 4 and 5 were evaluated retrospectively by two radiologists with different prostate imaging experiences. The images were grouped into two data sets. Dataset-1 was bpMRI, and dataset-2 was mpMRI. Two radiologists first evaluated dataset-1 independently of each other, and 1 month later, dataset-2. They recorded whether there was an invasion and where it was seen in the patients. Then, the results were compared. Results: A total of 75 patients were included in the study. Periprostatic invasion was detected in 33 of the patients. Both the 1st reader and the 2nd reader image detected all the cases with invasion (100%) separately between dataset-1 and set-2. Compatibility for image dataset-1 and dataset-2 between both readers was observed to be excellent. Conclusions: There is no need to use contrast agent to evaluate periprostatic invasion and to have an idea about local staging in PCa patients.

Objetivo: Nuestro estudio tiene como objetivo demostrar la detección de la invasión por resonancia magnética biparamétrica de próstata (BPMRI). Material y métodos: Los casos cuyo diagnóstico histopatológico fue PCA y cuyo informe MPMRI se informó como Pirads 4 y 5 fueron evaluados retrospectivamente por dos radiólogos con diferentes experiencias de imágenes de próstata. Las imágenes se agruparon en dos conjuntos de datos. DataSet-1 fue BPMRI, DataSet-2 fue MPMRI. Dos radiólogos evaluaron por primera vez el conjunto de datos 1 independientemente el uno del otro, y 1 mes después, el conjunto de datos-2. Registraron si había una invasión y dónde se vio en los pacientes. Luego se compararon los resultados. Resultados: Se incluyeron un total de 75 pacientes en el estudio. La invasión periprostática se detectó en 33 de los pacientes. Tanto el primer lector como la imagen del segundo lector detectaron todos los casos con invasión (100%) por separado entre el conjunto de datos-1 y el set-2. Se observó que la compatibilidad para el conjunto de datos de imágenes-1 y el conjunto de datos entre ambos lectores era excelente. Conclusiones: No es necesario usar el agente de contraste para evaluar la invasión periprostática y tener una idea sobre la puesta en escena local en pacientes con PCA.

Novel Gadolinium-Free Ultrasmall Nanostructured Positive Contrast for Magnetic Resonance Angiography and Imaging.

Nanostructured contrast agents are promising alternatives to Gd3+-based chelates in magnetic resonance (MR) imaging techniques. A novel ultrasmall paramagnetic nanoparticle (UPN) was strategically designed to maximize the number of exposed paramagnetic sites and r1 while minimizing r2, by decorating 3 nm titanium dioxide nanoparticles with suitable amounts of iron oxide. Its relaxometric parameters are comparable to those of gadoteric acid (GA) in agar phantoms, and the r2/r1 ratio of 1.38 at 3 T is close to the ideal unitary value. The strong and prolonged contrast enhancement of UPN before renal excretion was confirmed by T1-weighted MR images of Wistar rats after intravenous bolus injection. Those results associated with good biocompatibility indicate its high potential as an alternative blood-pool contrast agent to the GA gold standard for MR angiography, especially for patients with severe renal impairment.

Hybrid Nanoparticles of Citrate-Coated Manganese Ferrite and Gold Nanorods in Magneto-Optical Imaging and Thermal Therapy.

The development of nanomaterials has drawn considerable attention in nanomedicine to advance cancer diagnosis and treatment over the last decades. Gold nanorods (GNRs) and magnetic nanoparticles (MNPs) have been known as commonly used nanostructures in biomedical applications due to their attractive optical properties and superparamagnetic (SP) behaviors, respectively. In this study, we proposed a simple combination of plasmonic and SP properties into hybrid NPs of citrate-coated manganese ferrite (Ci-MnFe2O4) and cetyltrimethylammonium bromide-coated GNRs (CTAB-GNRs). In this regard, two different samples were prepared: the first was composed of Ci-MnFe2O4 (0.4 wt%), and the second contained hybrid NPs of Ci-MnFe2O4 (0.4 wt%) and CTAB-GNRs (0.04 wt%). Characterization measurements such as UV-Visible spectroscopy and transmission electron microscopy (TEM) revealed electrostatic interactions caused by the opposing surface charges of hybrid NPs, which resulted in the formation of small nanoclusters. The performance of the two samples was investigated using magneto-motive ultrasound imaging (MMUS). The sample containing Ci-MnFe2O4_CTAB-GNRs demonstrated a displacement nearly two-fold greater than just using Ci-MnFe2O4; therefore, enhancing MMUS image contrast. Furthermore, the preliminary potential of these hybrid NPs was also examined in magnetic hyperthermia (MH) and photoacoustic imaging (PAI) modalities. Lastly, these hybrid NPs demonstrated high stability and an absence of aggregation in water and phosphate buffer solution (PBS) medium. Thus, Ci-MnFe2O4_CTAB-GNRs hybrid NPs can be considered as a potential contrast agent in MMUS and PAI and a heat generator in MH.

Segurança do Agente de Contraste SF6 (SonoVueⓇ) no Ecocardiograma sob Estresse Farmacológico / Safety of SF6(SonoVue®) Contrast Agent on Pharmacological Stress Echocardiogram

Resumo Fundamento Em 2007, a Food and Drug Administration (FDA) determinou revisões sobre segurança dos agentes de contraste ecocardiográfico (ACE) disponíveis no mercado após relatos de mortes. Ao longo desses anos, diversos estudos comprovaram a segurança dos ACE, porém com poucos estudos relacionados ao SonoVue®. Objetivos Avaliar a segurança do SonoVue® durante o ecocardiograma sob estresse farmacológico (EEF) por meio da análise da incidência de reações alérgicas e da comparação entre os grupos quanto ao surgimento de arritmia, efeitos colaterais menores e eventos adversos. Métodos Estudo observacional, prospectivo, no qual 2.346 pacientes foram submetidos ao EEF e divididos em dois grupos: grupo 1 com ACE (n=1.099) e grupo 2 sem ACE (n=1.247). Os pacientes foram avaliados durante o EEF - 24 horas e 30 dias. Foi definido p significativo quando <0,05. Resultados O grupo 1 apresentou efeitos colaterais mais leves, como cefaleia (5/0,5% vs. 19/1,5%, p=0,012) e hipertensão reativa (3/0,3% vs . 19/1,5%, p=0,002), menos arritmias como extrassístoles ventriculares (180/16,4% vs . 247/19,8%, p=0,032) e taquicardia paroxística supraventricular (2/0,2% vs . 15/1,2%, p=0,003), assim como nenhum evento adverso como infarto agudo do miocárdio (IAM) e óbito. No grupo 2, um paciente apresentou IAM <24h (1/01%) e dois óbitos <30 dias (2/0,1%). Urticária relacionada ao SonoVue® foi observada em 3 (0,3%) pacientes sem reação anafilática. Conclusão SonoVue® demonstrou segurança durante o EEF, não sendo observados morte, IAM ou reação anafilática. Observou-se menor incidência de efeitos colaterais mais leves e arritmias no grupo que utilizou o ACE, assim como baixa incidência de reações alérgicas leves.

Abstract Background In 2007, the United States Food and Drug Administration mandated safety reviews of commercially available echocardiographic contrast agents (ECA), following reports of death. During the past years, different studies have proven the safety of ECA, but there have been few studies on SonoVue®. Objectives To evaluate the safety of SonoVue® during pharmacological stress echocardiography (PSE), by analyzing the incidence of allergic reactions and comparing groups regarding the appearance of arrhythmia, minor side effects and adverse events. Methods In this observational, prospective study, 2346 patients underwent PSE, and they were divided into the following 2 groups: group 1 with ECA (n = 1099) and group 2 without ECA (n = 1247). Patients were evaluated during PSE, at 24 hours, and at 30 days. Statistical significance was defined as p < 0.05. Results Group 1 had fewer minor side effects, such as headache (5/0.5% versus 19/1.5%, p = 0.012) and less reactive hypertension (3/0.3% versus 19/1.5%, p = 0.002); fewer arrhythmias, such as ventricular extrasystoles (180/16.4% versus 247/19.8%, p = 0.032) and paroxysmal supraventricular tachycardia (2/0.2% versus 15/1.2%, p = 0.003); and no adverse events, such as acute myocardial infarction (AMI) or death. In group 2, 1 patient had AMI in < 24 hours (1/01%), and there were 2 deaths in < 30 days (2/0.1%). SonoVue®-related urticaria was seen in 3 (0.3%) patients, without anaphylactic reaction. Conclusion SonoVue® demonstrated safety during PSE. No cases of death, AMI, or anaphylactic reaction were observed. There was a lower incidence of minor side effects and arrhythmias in the group that received ECA, as well as a low incidence of mild allergic reactions.

The contrast agent 2,3,5-triiodobenzoic acid (TIBA) induces cell death in tumor cells through the generation of reactive oxygen species.

The 2,3,5-triiodobenzoic acid (TIBA) is an iodine contrast agent used for visualization of tissue in X-ray techniques. However, TIBA induces physiological complications like increase in oxygen reactive species (ROS), and consequently, contrast-induced nephropathies. TIBA's antitumor activity was demonstrated in lung cancer, but the subcellular mechanisms involving its activity in tumor cells are still unknown. Thus, the objective of this work was evaluate whether the anti-tumor activity of TIBA involves ROS increase, in tumor lines of non-small cell lung cancer (H460), chronic myeloid leukemia (K562), and its cytotoxicity in normal renal epithelial (VERO). The MTT (3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide) assay was used for evaluation of cell viability, the H2DCFDA (cell-permeant 2',7'-dichlorodihydrofluorescein diacetate) fluorescent probe to evaluate ROS induction, cell cycle analysis was performed using flow cytometry to measure cell death, and immunofluorescence with annexin/7-AAD (7-amino-actinomycin D), to assess the association of cell death with the ROS generation. TIBA decreases cell viability in a dose-dependent manner for the H460 and K562. However, VERO cells showed less response to the drug, with 70% viable cells after 72 h of treatment in the highest concentration of the drug. While the tumor cells with only 20% viable cells. Besides, tumor cells exhibited higher DNA fragmentation, compared to the renal line (VERO with 5% of fragmented DNA, H460 with 26%, and 56% in K562). Finally, TIBA-induced ROS increase and apoptosis in all lines, which is significantly decreased after treatment with the antioxidant N-acetyl-cysteine (NAC). These data demonstrate the relationship between the increased cellular oxidative stress and the anti-tumor action of the TIBA.

In vitro and in vivo comparative performance studies of gadolinium-loaded zeolites and Gd-DOTA as contrast agents for MRI applications.

Gadolinium-based contrast agents (CAs) were synthesized using faujasite zeolite (NaX) and zeolite beta (BEA) and their performances in vitro and in vivo were compared to the widely used commercial CA, gadoteric acid (Gd-DOTA). Magnetic resonance imaging (MRI) relaxometry studies (considering longitudinal [T1 ] and transverse [T2 ] relaxation times) were performed using Gd-DOTA and the zeolitic materials loaded with Gd3+ . The Gd-loaded NaX, which presented large pores and cavities (7.35 and 11.24 Å, respectively), exhibited relaxivity values of around 52 mM-1 s-1 , while BEA, which presented smaller pore and cavity diameters (5.95 and 6.68 Å, respectively) showed lower relaxivity values of ~4.8 mM-1 s-1 . The effect of the Gd-loaded NaX as MRI CA was tested in vivo in Sprague-Dawley rats, employing a 7 T scanner, with comparison to Gd-DOTA MRI angiography. The relaxivity measurements showed that the Gd-loaded NaX (50 mM-1 s-1 ) provided better image contrast than Gd-DOTA (5.1 mM-1 s-1 ). Clearance studies of the CAs using urine and blood showed that both Gd-loaded NaX and Gd-DOTA were eliminated from the body after 2 days, demonstrating the potential of Gd-loaded NaX for use as an MRI CA.

Presence of other rare earth metals in gadolinium-based contrast agents.

Gadolinium-based contrast agents (GBCA) are widely used to enhance tissue contrast during magnetic resonance imaging (MRI) procedures. However, free Gadolinium (Gd) is undesirable as a drug substance, due to its high toxicity. Consequently, a coordinating ligand is required to keep it in solution and to increase tolerance. In order to achieve an adequate performance, GBCA must be administered in relatively large amounts. Chelate amounts are around 13-20 g and for Gd alone, this may amount to 3.3 g. Taking into account the route of administration, impurities in GBCA may be significant. Gadolinium occurs in nature along with 16 other elements known collectively as rare earth metals (RE), which are found throughout the earth's crust in minerals such as monazite. Gadolinium oxide corresponds to 0.7-4.0% of the RE present in minerals, and the sum concentration of RE in minerals is around 4%. Rare earth metals are difficult to separate, as the chemical and physical properties of one RE are significantly similar to those of others. In this study, the presence of other RE in GBCA formulations was investigated. Different lots of Magnevist®, Viewgam®, OptiMARK®, Omniscan®, Dotarem®, and Gadovist® were analyzed. Inductively-coupled plasma mass spectrometry and atomic absorption spectrometry were used for RE determination. Procedure optimization included sample decomposition and method validation for element determination. The results showed that Sc, Y, La, Ce, Pr, Nd, Eu, Tb, Tm, Dy, Ho, and Er were present in the 22 samples analyzed. Terbium, Thulium, Europium, and Lanthanum were, on average, found in the highest amounts, which were 0.42 mg/L, 0.17 mg/L, 0.17 mg/L, and 0.16 mg/L, respectively. These results could be attributed to the similarity among Europium, Gadolinium, and Terbium. They are in sequence in the periodic table and therefore present very close ionic radii, restricting their separation. Considering the sum of all RE, Viewgam® was the most contaminated formulation (mean of 2.16 mg/L) and Magnevist® the least (mean of 0.64 mg/L). Although the RE are chemically similar, the other RE do not perform as Gd as a contrast agent; therefore, their presence in formulations may be a matter of concern.

Frequency response curves for a Mooney-Rivlin hyperelastic microbubble oscillating as a contrast agent in an acoustic pressure field.

In this work, we have developed numerical simulations and weakly nonlinear analysis based on the multiple-scales perturbation technique for a coated microbubble that performs radial pulsations subject to an acoustic pressure disturbance in the far-field and whose encapsulated hyperelastic material obeys the Mooney-Rivlin equation. Departing from an elastic coating as a hyperelastic shell of finite thickness, we assume eventually that the shell is of very small thickness in comparison with the microbubble radius. Under this condition, we then perform weakly nonlinear analysis, to identify resonance conditions for small pressure disturbances of the acoustic field. In parallel and also for the limit of small thickness, we have carried out numerical simulations of the radial motion of the microbubble, identifying the onset of limit cycles via the construction of Poincare maps. Under both schemes, we have recognized the importance of two dimensionless hyperelastic parameters that dictate the main behavior of the oscillations: α∗ and ß∗. Decreasing the values of these parameters, the resonance conditions are drastically amplified, which is an expected result because of the weak rigidity of the hyperelastic solid, prevails. In this manner, we suggest that moderate values for these previous parameters can be widely advisable when, in medical diagnostic applications, we are applying microbubbles as contrast agents. Therefore, we recommend widely the use of shell softens, because in this case the amplitude of radial pulsation is always amplified.

Gadolinium-containing carbon nanomaterials for magnetic resonance imaging: Trends and challenges.

Gadolinium-containing carbon nanomaterials are a new class of contrast agent for magnetic resonance imaging. They are characterized by a superior proton relaxivity to any current commercial gadolinium contrast agent and offer the possibility to design multifunctional contrasts. Intense efforts have been made to develop these nanomaterials because of their potential for better results than the available gadolinium contrast agents. The aim of the present work is to provide a review of the advances in research on gadolinium-containing carbon nanomaterials and their advantages over conventional gadolinium contrast agents. Due to their enhanced proton relaxivity, they can provide a reliable imaging contrast for cells, tissues or organs with much smaller doses than currently used in clinical practice, thus leading to reduced toxicity (as shown by cytotoxicity and biodistribution studies). Their active targeting capability allows for improved MRI of molecular or cellular targets, overcoming the limited labelling capability of available contrast agents (restricted to physiological irregularities during pathological conditions). Their potential of multifunctionality encompasses multimodal imaging and the combination of imaging and therapy.

Açai juice as contrast agent in MRCP exams: qualitative and quantitative image evaluation

Abstract This works aims to assess images obtained with administration of açai juice as compared to a manufactured standard iron oxide-based contrast employed as negative oral agents in Magnetic Resonance Cholangiopancreatography (MRCP), employing qualitative and quantitative evaluation. The research was developed with 64 patients submitted to MRCP exams (on 2 days) in a clinic of Curitiba city (Brazil). First (day 1), a manufactured iron oxide-based contrast (A) was offered and later (day 2), açai juice (contrast B) was given to patients. Radiologists (R1 and R2) evaluated the images, classifying them by a score (1-4). In order to have a quantitative assessment, Image J free software was employed generating plots of gray levels against distance of a chosen area of the bile duct interest region. Evaluating images for contrast A, R1 furnished an average score of 3.52 and R2 of 3.27. For contrast B, R1 provided 3.44 and R2 3.38. Both evaluators considered image quality with contrast A adequate for 62 patients. R1 considered adequate for 62 and R2 for 60 patients when using açai juice. By taking same images for all patients with Image J, a quantitative analysis was obtained, resulting correlation coefficient of 0.986 between average curves of contrasts A and B. Thus, açai juice is an adequate alternative as contrast agent in MRCP exams. Image J was employed as a new method for quantitative investigation of image quality, presenting good agreement with medical opinion.

TiO2 -coated fluoride nanoparticles for dental multimodal optical imaging.

Core-shell nanostructures associated with photonics techniques have found innumerous applications in diagnostics and therapy. In this work, we introduce a novel core-shell nanostructure design that serves as a multimodal optical imaging contrast agent for dental adhesion evaluation. This nanostructure consists of a rare-earth-doped (NaYF4 :Yb 60%, Tm 0.5%)/NaYF4 particle as the core (hexagonal prism, ~51 nm base side length) and the highly refractive TiO2 material as the shell (~thickness of 15 nm). We show that the TiO2 shell provides enhanced contrast for optical coherence tomography (OCT), while the rare-earth-doped core upconverts excitation light from 975 nm to an emission peaked at 800 nm for photoluminescence imaging. The OCT and the photoluminescence wide-field images of human tooth were demonstrated with this nanoparticle core-shell contrast agent. In addition, the described core-shell nanoparticles (CSNps) were dispersed in the primer of a commercially available dental bonding system, allowing clear identification of dental adhesive layers with OCT. We evaluated that the presence of the CSNp in the adhesive induced an enhancement of 67% scattering coefficient to significantly increase the OCT contrast. Moreover, our results highlight that the upconversion photoluminescence in the near-infrared spectrum region is suitable for image of deep dental tissue.

Study on the Correlation between Barium Radiography and Pulmonary Infection rate in the Evaluation of Swallowing Function

OBJECTIVES: To compare the results respectively obtained from the utilization of 60% barium sulfate suspension and Iohexol as contrast agents for videofluoroscopic swallowing studies and the relationship between the clinical application of the two kinds of contrast agents and the incidence of pneumonia. METHODS: Sixty cases of stroke patients with dysphagia were selected in rehabilitation department of our hospital, and the gender, age, position of the disease, and stroke nature between groups had no significant difference. Among which, 30 patients who were administered 350 mgI/ml Iohexol, and the other 30 patients with 60% barium sulfate suspension as contrast agent. We performed videofluoroscopic swallowing studies with barium 60% versus Iohexol within 1 week after admission and 2 weeks after admission. RESULTS: After 2 weeks in hospital, the aspiration pneumonia incidence of two groups was statistically significant (p<0.05), the pneumonia incidence of Iohexol group was lower than barium sulfate group which might have a impossble relevance with barium aspiration. CONCLUSIONS: During the videofluoroscopic swallowing study of dysphagia after stroke, barium sulfate can enhance the pneumonia incidence, and Iohexol can be widely applied in videofluoroscopic swallowing study.

Chitosan-coated microvesicles: Effect of polysaccharide-phospholipid affinity on decafluorobutane dissolution.

The stability of perfluorinated microvesicles is mainly determined by the presence of interfacial materials and their ability to hinder the gas component diffusibility into the bloodstream. The goal of this study is to increase the persistence of the gaseous-core by introducing chitosan-coated 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) microvesicles, reducing gas diffusion from microvesicles, and increasing for a long time ultrasonic signals. Our hypothesis was based on the irreversible adhesion of chitosan towards DSPC head groups observed in thin-films models. This affinity enhanced the stabilization of gaseous-core microvesicles, in which the polysaccharide effectively reduced the phospholipid phase transition enthalpy from 383±5.5Jmg(-1) for plain to 150±9.7Jmg(-1) for chitosan-coated microvesicles, providing a more stable structure that diminished the gaseous component lost and provided the persistence of intense (19)F-NMR signals after 48h, twice as long compared to plain samples. As a result, stronger and long-lasting ultrasonic signals were produced by the more stable chitosan-containing microvesicles, thus, presenting great potential to increase the diagnostic and therapeutic applications of perfluorocarbon carries.

Ultrasmall cationic superparamagnetic iron oxide nanoparticles as nontoxic and efficient MRI contrast agent and magnetic-targeting tool.

Fully dispersible, cationic ultrasmall (7 nm diameter) superparamagnetic iron oxide nanoparticles, exhibiting high relaxivity (178 mM(-1)s(-1) in 0.47 T) and no acute or subchronic toxicity in Wistar rats, were studied and their suitability as contrast agents for magnetic resonance imaging and material for development of new diagnostic and treatment tools demonstrated. After intravenous injection (10 mg/kg body weight), they circulated throughout the vascular system causing no microhemorrhage or thrombus, neither inflammatory processes at the mesentery vascular bed and hepatic sinusoids (leukocyte rolling, adhesion, or migration as evaluated by intravital microscopy), but having been spontaneously concentrated in the liver, spleen, and kidneys, they caused strong negative contrast. The nanoparticles are cleared from kidneys and bladder in few days, whereas the complete elimination from liver and spleen occurred only after 4 weeks. Ex vivo studies demonstrated that cationic ultrasmall superparamagnetic iron oxide nanoparticles caused no effects on hepatic and renal enzymes dosage as well as on leukocyte count. In addition, they were readily concentrated in rat thigh by a magnet showing its potential as magnetically targeted carriers of therapeutic and diagnostic agents. Summarizing, cationic ultrasmall superparamagnetic iron oxide nanoparticles are nontoxic and efficient magnetic resonance imaging contrast agents useful as platform for the development of new materials for application in theranostics.

Dual responsive dysprosium-doped hydroxyapatite particles and toxicity reduction after functionalization with folic and glucuronic acids.

The development of probes for biomedical applications demands materials with low toxicity levels besides fluorescence or magnetic properties to be detected by confocal microscopes or MRI resonators. Several drug delivery systems or other biomedical materials prepared with hydroxyapatite have been proposed, however, toxicity effects might arise when the size of particles is nanometric. In this study, hydroxyapatite functionalized with glucuronic or folic acids presented lower oxidative stress, measured from lipoperoxides and nitric oxide indicators in rats than pure hydroxyapatite. In separated experiments, hydroxyapatite was doped with dysprosium cations by coprecipitation producing a single crystal phase with fluorescent properties easily visualized by confocal microscopy when excited at 488nm. These particles also presented the ability to modify the proton relaxation time in T1 maps collected by magnetic resonance imaging. These modified hydroxyapatite nanoparticles could be candidates to design bimodal probes with low toxicity.

Monte Carlo modeling of converging small-field contrast-enhanced radiotherapy of prostate.

Radiation therapy using a kilovoltage X-ray source to irradiate a target previously loaded with a radiological contrast agent, contrast-enhanced radiotherapy (CERT), has been shown both theoretically and in a preliminary experimental study to represent a potential alternative to high-energy treatments. It has also been shown, however, to produce an integral dose that can be up to twice that resulting from a conventional megavoltage treatment. In this work, using a realistic patient model and Monte Carlo simulation, a CERT prostate treatment plan is designed that makes use of a plurality of small circular beams aimed at the target in such a way as to minimize the radiological trajectory to the target volume. Gold nanoparticles are assumed to be the contrast agent. Two cases are examined, one with a concentration level in the target of 10 mg-Au per gram of tissue and the second with a concentration of 3 mg-Au per gram of tissue in the target. A background concentration of 1 mg of contrast agent per gram of tissue was assumed everywhere else in both cases. The Cimmino feasibility algorithm was then used to find each beam weight in order to obtain the prescribed target dose, set at 72 Gy to 100% of the tumor volume. It is shown that the approach using the small circular fields, a radiosurgery treatment, produces treatment plans with excellent absorbed dose distributions while at the same time it reduces by up to 60% the non-tumor integral dose imparted to the irradiated subject. A brief discussion on the technology necessary to clinically implement this treatment modality is also presented.