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1.
Theranostics ; 10(3): 968-997, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31938046

RESUMO

Despite recent advances in the translation of therapeutic nanoparticles (TNPs) into the clinic, the field continues to face challenges in predictably and selectively delivering nanomaterials for the treatment of solid cancers. The concept of enhanced permeability and retention (EPR) has been coined as a convenient but simplistic descriptor of high TNP accumulation in some tumors. However, in practice EPR represents a number of physiological variables rather than a single one (including dysfunctional vasculature, compromised lymphatics and recruited host cells, among other aspects of the tumor microenvironment) - each of which can be highly heterogenous within a given tumor, patient and across patients. Therefore, a clear need exists to dissect the specific biophysical factors underlying the EPR effect, to formulate better TNP designs, and to identify patients with high-EPR tumors who are likely to respond to TNP. The overall pharmacology of TNP is governed by an interconnected set of spatially defined and dynamic processes that benefit from a systems-level quantitative approach, and insights into the physiology have profited from the marriage between in vivo imaging and quantitative systems pharmacology (QSP) methodologies. In this article, we review recent developments pertinent to image-guided systems pharmacology of nanomedicines in oncology. We first discuss recent developments of quantitative imaging technologies that enable analysis of nanomaterial pharmacology at multiple spatiotemporal scales, and then examine reports that have adopted these imaging technologies to guide QSP approaches. In particular, we focus on studies that have integrated multi-scale imaging with computational modeling to derive insights about the EPR effect, as well as studies that have used modeling to guide the manipulation of the EPR effect and other aspects of the tumor microenvironment for improving TNP action. We anticipate that the synergistic combination of imaging with systems-level computational methods for effective clinical translation of TNPs will only grow in relevance as technologies increase in resolution, multiplexing capability, and in the ability to examine heterogeneous behaviors at the single-cell level.

2.
Vet Ophthalmol ; 23(1): 148-159, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31364808

RESUMO

OBJECTIVE: To retrospectively describe laboratory findings, treatment, and outcome associated with equine infectious keratitis in Finland. ANIMALS AND PROCEDURES: Medical records of horses diagnosed with infectious keratitis in University of Helsinki Equine Hospital from January 2007 to June 2018 were reviewed. RESULTS: Forty-seven cases were included. Keratomycosis was diagnosed in 27 eyes and bacterial keratitis in 20 eyes. Aspergillus flavus was the most frequent fungal isolate (9/17, 53%), followed by Cylindrocarpon sp. (3/17, 18%) and Aspergillus fumigatus (2/17, 12%). Susceptibility was tested for 10/11 Aspergillus sp. isolates; all were susceptible to voriconazole while only two were susceptible to amphotericin B. Cylindrocarpon sp. isolates were resistant to both agents. Streptococcus equi subsp. zooepidemicus was the most frequent bacterial isolate (9/19, 47%), followed by other streptococci (4/19, 21%). All 13 Streptococcus sp. isolates were susceptible to penicillin, and all tested isolates (n = 11) were also susceptible to chloramphenicol. Mean duration of medical treatment was longer in fungal keratitis (38 days) than in bacterial keratitis (25 days) (P < .001). Twenty-six of the eyes underwent globe-sparing surgery in addition to medical therapy. Recovery was achieved in 66% (31/47) of all cases and in 59% (16/27) and 75% (15/20) (P = .264) of cases with keratomycosis and bacterial keratitis, respectively. CONCLUSIONS: Although Aspergillus sp. and S zooepidemicus were the most frequently encountered isolates, cytology, culture, and susceptibility testing are essential to differentiate bacterial and fungal keratitis and guide the clinician to choose the most efficient treatment.

3.
Angew Chem Int Ed Engl ; 58(52): 18864-18867, 2019 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-31657088

RESUMO

Intriguing reports of enhanced diffusion in enzymes and molecular catalysts have spurred significant interest in experimental and theoretical investigations, and the mechanism of this phenomenon is the topic of lively debate. Here we use time-resolved diffusion NMR methods to measure the diffusion coefficients (D) of small molecule species involved in chemical reactions with high temporal resolution. We show the enhanced diffusion of small molecules cannot be explained by reaction velocity, and that apparent measurements of enhanced diffusion by small molecules appear to be caused by bulk fluid flow processes such as convection.

5.
Clin Nucl Med ; 44(5): 414-416, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30829870

RESUMO

Extraosseous Tc-MDP uptake on bone scans is frequently encountered and has a broad differential diagnosis. A small subset of such patients can present with intestinal Tc-MDP uptake. We present the case of a 35-year-old woman with status after right nephrectomy for renal cell carcinoma, being followed with bone scan for osseous metastases. Follow-up imaging revealed new faint Tc-MDP uptake in the right hemiabdomen. Correlation with contrast-enhanced CT localized this uptake to the ascending colon. Enteric Tc-MDP uptake and its association with iodinated contrast should be considered in the differential diagnosis of extraosseous enteric Tc-MDP uptake.


Assuntos
Neoplasias Ósseas/diagnóstico por imagem , Colo/diagnóstico por imagem , Neoplasias Renais/patologia , Tomografia Computadorizada por Raios X , Adulto , Neoplasias Ósseas/secundário , Meios de Contraste , Diagnóstico Diferencial , Feminino , Humanos , Compostos Radiofarmacêuticos , Medronato de Tecnécio Tc 99m
6.
Chemphyschem ; 20(7): 926-930, 2019 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-30776189

RESUMO

A general procedure for measurement of time-resolved diffusion coefficients of molecular species by NMR is described, including the use of methanol for fast temperature-independent gradient calibration.

7.
ACS Nano ; 12(12): 12015-12029, 2018 12 26.
Artigo em Inglês | MEDLINE | ID: mdl-30508377

RESUMO

Tumor-associated macrophages (TAMs) are widely implicated in cancer progression, and TAM levels can influence drug responses, particularly to immunotherapy and nanomedicines. However, it has been difficult to quantify total TAM numbers and their dynamic spatiotemporal distribution in a non-invasive and translationally relevant manner. Here, we address this need by developing a pharmacokinetically optimized, 64Cu-labeled polyglucose nanoparticle (Macrin) for quantitative positron emission tomography (PET) imaging of macrophages in tumors. By combining PET with high-resolution in vivo confocal microscopy and ex vivo imaging of optically cleared tissue, we found that Macrin was taken up by macrophages with >90% selectivity. Uptake correlated with the content of macrophages in both healthy tissue and tumors ( R2 > 0.9) and showed striking heterogeneity in the TAM content of an orthotopic and immunocompetent mouse model of lung carcinoma. In a proof-of-principle application, we imaged Macrin to monitor the macrophage response to neo-adjuvant therapy, using a panel of chemotherapeutic and γ-irradiation regimens. Multiple treatments elicited 180-650% increase in TAMs. Imaging identified especially TAM-rich tumors thought to exhibit enhanced permeability and retention of nanotherapeutics. Indeed, these TAM-rich tumors accumulated >700% higher amounts of a model poly(d,l-lactic- co-glycolic acid)- b-polyethylene glycol (PLGA-PEG) therapeutic nanoparticle compared to TAM-deficient tumors, suggesting that imaging may guide patient selection into nanomedicine trials. In an orthotopic breast cancer model, chemoradiation enhanced TAM and Macrin accumulation in tumors, which corresponded to the improved delivery and efficacy of two model nanotherapies, PEGylated liposomal doxorubicin and a TAM-targeted nanoformulation of the toll-like receptor 7/8 agonist resiquimod (R848). Thus, Macrin imaging offers a selective and translational means to quantify TAMs and inform therapeutic decisions.


Assuntos
Antibióticos Antineoplásicos/farmacologia , Doxorrubicina/farmacologia , Glucanos/química , Marcação por Isótopo , Neoplasias Pulmonares/tratamento farmacológico , Macrófagos/efeitos dos fármacos , Nanopartículas/química , Animais , Radioisótopos de Cobre , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Neoplasias Pulmonares/diagnóstico por imagem , Macrófagos/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos NOD , Camundongos Knockout , Terapia Neoadjuvante , Tomografia por Emissão de Pósitrons
9.
Chem Commun (Camb) ; 52(93): 13576-13579, 2016 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-27805187

RESUMO

We report photochromic donor-acceptor Stenhouse adducts (DASAs) capable of fully reversible photoisomerization with visible light in organic solvents including chloroform, acetonitrile and benzene. The rates of photoisomerization and thermal reversion can be tuned by altering the electronics of the donor adduct. X-Ray crystallography and photo-NMR experiments unambiguously establish molecular structures.

10.
Arch Biochem Biophys ; 606: 26-33, 2016 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-27431058

RESUMO

Although oxidative stress is known to impede the tricarboxylic acid (TCA) cycle and oxidative phosphorylation, the nutritionally-versatile microbe, Pseudomonas fluorescens has been shown to proliferate in the presence of hydrogen peroxide (H2O2) and nitrosative stress. In this study we demonstrate the phospho-transfer system that enables this organism to generate ATP was similar irrespective of the carbon source utilized. Despite the diminished activities of enzymes involved in the TCA cycle and in the electron transport chain (ETC), the ATP levels did not appear to be significantly affected in the stressed cells. Phospho-transfer networks mediated by acetate kinase (ACK), adenylate kinase (AK), and nucleoside diphosphate kinase (NDPK) are involved in maintaining ATP homeostasis in the oxidatively-challenged cells. This phospho-relay machinery orchestrated by substrate-level phosphorylation is aided by the up-regulation in the activities of such enzymes like phosphoenolpyruvate carboxylase (PEPC), pyruvate orthophosphate dikinase (PPDK), and phosphoenolpyruvate synthase (PEPS). The enhanced production of phosphoenolpyruvate (PEP) and pyruvate further fuel the synthesis of ATP. Taken together, this metabolic reconfiguration enables the organism to fulfill its ATP need in an O2-independent manner by utilizing an intricate phospho-wire module aimed at maximizing the energy potential of PEP with the participation of AMP.


Assuntos
Trifosfato de Adenosina/química , Pseudomonas fluorescens/metabolismo , Monofosfato de Adenosina/química , Ciclo do Ácido Cítrico , Densitometria , Transporte de Elétrons , Homeostase , Peróxido de Hidrogênio/química , Lipídeos/química , Oxirredução , Fosforilação Oxidativa , Estresse Oxidativo , Oxigênio/química , Fosfoenolpiruvato/química , Fosforilação , Fosfotransferases (Aceptores Pareados)/metabolismo , Piruvato Ortofosfato Diquinase/metabolismo , Espécies Reativas de Oxigênio/metabolismo
11.
Magn Reson Med ; 75(5): 1967-77, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26077645

RESUMO

PURPOSE: To determine optimal parameters for acquisition and processing of dynamic contrast-enhanced MRI (DCE-MRI) to detect small changes in near normal low blood-brain barrier (BBB) permeability. METHODS: Using a contrast-to-noise ratio metric (K-CNR) for Ktrans precision and accuracy, the effects of kinetic model selection, scan duration, temporal resolution, signal drift, and length of baseline on the estimation of low permeability values was evaluated with simulations. RESULTS: The Patlak model was shown to give the highest K-CNR at low Ktrans . The Ktrans transition point, above which other models yielded superior results, was highly dependent on scan duration and tissue extravascular extracellular volume fraction (ve ). The highest K-CNR for low Ktrans was obtained when Patlak model analysis was combined with long scan times (10-30 min), modest temporal resolution (<60 s/image), and long baseline scans (1-4 min). Signal drift as low as 3% was shown to affect the accuracy of Ktrans estimation with Patlak analysis. CONCLUSION: DCE acquisition and modeling parameters are interdependent and should be optimized together for the tissue being imaged. Appropriately optimized protocols can detect even the subtlest changes in BBB integrity and may be used to probe the earliest changes in neurodegenerative diseases such as Alzheimer's disease and multiple sclerosis.


Assuntos
Barreira Hematoencefálica , Meios de Contraste/química , Imagem por Ressonância Magnética/métodos , Permeabilidade , Adulto , Idoso , Algoritmos , Doença de Alzheimer/diagnóstico por imagem , Simulação por Computador , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Cinética , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/diagnóstico por imagem , Doenças Neurodegenerativas/diagnóstico por imagem , Distribuição Normal , Reprodutibilidade dos Testes , Processamento de Sinais Assistido por Computador , Adulto Jovem
12.
BMC Med Imaging ; 15: 19, 2015 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-26076957

RESUMO

BACKGROUND: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a promising technique to characterize pathology and evaluate treatment response. However, analysis of DCE-MRI data is complex and benefits from concurrent analysis of multiple kinetic models and parameters. Few software tools are currently available that specifically focuses on DCE-MRI analysis with multiple kinetic models. Here, we developed ROCKETSHIP, an open-source, flexible and modular software for DCE-MRI analysis. ROCKETSHIP incorporates analyses with multiple kinetic models, including data-driven nested model analysis. RESULTS: ROCKETSHIP was implemented using the MATLAB programming language. Robustness of the software to provide reliable fits using multiple kinetic models is demonstrated using simulated data. Simulations also demonstrate the utility of the data-driven nested model analysis. Applicability of ROCKETSHIP for both preclinical and clinical studies is shown using DCE-MRI studies of the human brain and a murine tumor model. CONCLUSION: A DCE-MRI software suite was implemented and tested using simulations. Its applicability to both preclinical and clinical datasets is shown. ROCKETSHIP was designed to be easily accessible for the beginner, but flexible enough for changes or additions to be made by the advanced user as well. The availability of a flexible analysis tool will aid future studies using DCE-MRI. A public release of ROCKETSHIP is available at https://github.com/petmri/ROCKETSHIP .


Assuntos
Algoritmos , Aumento da Imagem/métodos , Interpretação de Imagem Assistida por Computador/métodos , Imagem por Ressonância Magnética/métodos , Software , Interface Usuário-Computador , Humanos , Armazenamento e Recuperação da Informação/métodos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Desenho de Programas de Computador
13.
J Nutr Health Aging ; 19(1): 58-63, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25560817

RESUMO

The brain is one of the most energy-demanding organs in the body. It has evolved intricate metabolic networks to fulfill this need and utilizes a variety of substrates to generate ATP, the universal energy currency. Any disruption in the supply of energy results in various abnormalities including Alzheimer's disease (AD), a condition with markedly diminished cognitive ability. Astrocytes are an important participant in maintaining the cerebral ATP budget. However, under oxidative stress induced by numerous factors including aluminum toxicity, the ability of astroctyes to generate ATP is impaired due to dysfunctional mitochondria. This leads to globular, glycolytic, lipogenic and ATP-deficient astrocytes, cerebral characteristics common in AD patients. The reversal of these perturbations by such natural metabolites as pyruvate, α-ketoglutarate, acetoacetate and L-carnitine provides valuable therapeutic cues against AD.


Assuntos
Doença de Alzheimer/dietoterapia , Doença de Alzheimer/metabolismo , Encéfalo/metabolismo , Acetoacetatos/metabolismo , Acetoacetatos/uso terapêutico , Trifosfato de Adenosina/deficiência , Trifosfato de Adenosina/metabolismo , Alumínio/toxicidade , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Astrócitos/patologia , Encéfalo/citologia , Encéfalo/efeitos dos fármacos , Carnitina/metabolismo , Carnitina/uso terapêutico , Humanos , Ácidos Cetoglutáricos/metabolismo , Ácidos Cetoglutáricos/uso terapêutico , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Estresse Oxidativo/efeitos dos fármacos , Ácido Pirúvico/metabolismo , Ácido Pirúvico/uso terapêutico
14.
Pancreatology ; 15(1): 88-93, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25500342

RESUMO

Pancreatic pseudocyst is a relatively common occurrence resulting from acute or chronic pancreatitis. However, a rare subset of these patients present with a pseudocyst fistulizing into the portal vein. We present the case of a 58 year-old woman with a rapidly expanding pancreatic pseudocyst with portal venous fistulization causing portal vein thrombosis, in addition to biliary and duodenal obstruction. The patient underwent surgical decompression with a cyst-gastrostomy and was well until one week post-operatively when she experienced massive gastrointestinal hemorrhage leading to her death. A review of the literature is presented and a treatment algorithm to manage patients with pancreatic pseudocyst to portal vein fistula is proposed.


Assuntos
Fístula Pancreática/etiologia , Pseudocisto Pancreático/complicações , Veia Porta , Fístula Vascular/etiologia , Algoritmos , Evolução Fatal , Feminino , Hemorragia Gastrointestinal/etiologia , Humanos , Pessoa de Meia-Idade , Fístula Pancreática/cirurgia , Pseudocisto Pancreático/cirurgia , Fístula Vascular/cirurgia
15.
J Biol Inorg Chem ; 19(2): 247-58, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24166283

RESUMO

The recent emergence of multimodality imaging, particularly the combination of PET and MRI, has led to excitement over the prospect of improving detection of disease. Iron oxide nanoparticles have become a popular platform for the fabrication of PET/MRI probes owing to their advantages of high MRI detection sensitivity, biocompatibility, and biodegradability. In this article, we report the synthesis of dextran-coated iron oxide nanoparticles (DIO) labeled with the positron emitter (64)Cu to generate a PET/MRI probe, and modified with maleic anhydride to increase the negative surface charge. The modified nanoparticulate PET/MRI probe (MDIO-(64)Cu-DOTA) bears repetitive anionic charges on the surface that facilitate recognition by scavenger receptor type A (SR-A), a ligand receptor found on activated macrophages but not on normal vessel walls. MDIO-(64)Cu-DOTA has an average iron oxide core size of 7-8 nm, an average hydrodynamic diameter of 62.7 nm, an r1 relaxivity of 16.8 mM(-1) s(-1), and an r 2 relaxivity of 83.9 mM(-1) s(-1) (37 °C, 1.4 T). Cell studies confirmed that the probe was nontoxic and was specifically taken up by macrophages via SR-A. In comparison with the nonmodified analog, the accumulation of MDIO in macrophages was substantially improved. These characteristics demonstrate the promise of MDIO-(64)Cu-DOTA for identification of vulnerable atherosclerotic plaques via the targeting of macrophages.


Assuntos
Compostos Férricos/química , Ativação de Macrófagos , Macrófagos/metabolismo , Imagem por Ressonância Magnética/métodos , Tomografia por Emissão de Pósitrons/métodos , Animais , Linhagem Celular , Radioisótopos de Cobre , Dextranos/química , Compostos Férricos/metabolismo , Compostos Férricos/toxicidade , Macrófagos/citologia , Nanopartículas/química , Tamanho da Partícula , Ratos , Propriedades de Superfície
16.
Clin Cancer Res ; 19(9): 2518-27, 2013 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-23532891

RESUMO

PURPOSE: Targeted nanotherapies are being developed to improve tumor drug delivery and enhance therapeutic response. Techniques that can predict response will facilitate clinical translation and may help define optimal treatment strategies. We evaluated the efficacy of diffusion-weighted magnetic resonance imaging to monitor early response to CRLX101 (a cyclodextrin-based polymer particle containing the DNA topoisomerase I inhibitor camptothecin) nanotherapy (formerly IT-101), and explored its potential as a therapeutic response predictor using a mechanistic model of tumor cell proliferation. EXPERIMENTAL DESIGN: Diffusion MRI was serially conducted following CRLX101 administration in a mouse lymphoma model. Apparent diffusion coefficients (ADCs) extracted from the data were used as treatment response biomarkers. Animals treated with irinotecan (CPT-11) and saline were imaged for comparison. ADC data were also input into a mathematical model of tumor growth. Histological analysis using cleaved-caspase 3, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, Ki-67, and hematoxylin and eosin (H&E) were conducted on tumor samples for correlation with imaging results. RESULTS: CRLX101-treated tumors at day 2, 4, and 7 posttreatment exhibited changes in mean ADC = 16 ± 9%, 24 ± 10%, 49 ± 17%, and size (TV) = -5 ± 3%, -30 ± 4%, and -45 ± 13%, respectively. Both parameters were statistically greater than controls [p(ADC) ≤ 0.02, and p(TV) ≤ 0.01 at day 4 and 7], and noticeably greater than CPT-11-treated tumors (ADC = 5 ± 5%, 14 ± 7%, and 18 ± 6%; TV = -15 ± 5%, -22 ± 13%, and -26 ± 8%). Model-derived parameters for cell proliferation obtained using ADC data distinguished CRLX101-treated tumors from controls (P = 0.02). CONCLUSIONS: Temporal changes in ADC specified early CRLX101 treatment response and could be used to model image-derived cell proliferation rates following treatment. Comparisons of targeted and nontargeted treatments highlight the utility of noninvasive imaging and modeling to evaluate, monitor, and predict responses to targeted nanotherapeutics.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Camptotecina/administração & dosagem , Ciclodextrinas/administração & dosagem , Imagem de Difusão por Ressonância Magnética , Linfoma/patologia , Animais , Linhagem Celular Tumoral , Feminino , Humanos , Linfoma/tratamento farmacológico , Camundongos , Camundongos Nus , Modelos Biológicos , Nanomedicina , Resultado do Tratamento , Carga Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Mar Pollut Bull ; 73(2): 470-84, 2013 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-23428288

RESUMO

To reduce the negative effect of climate change on Biodiversity, the use of geological CO2 sequestration has been proposed; however leakage from underwater storages may represent a risk to marine life. As extracellular homeostasis is important in determining species' ability to cope with elevated CO2, we investigated the acid-base and ion regulatory responses, as well as the density, of sea urchins living around CO2 vents at Vulcano, Italy. We conducted in situ transplantation and field-based laboratory exposures to different pCO2/pH regimes. Our results confirm that sea urchins have some ability to regulate their extracellular fluid under elevated pCO2. Furthermore, we show that even in closely-related taxa divergent physiological capabilities underlie differences in taxa distribution around the CO2 vent. It is concluded that species distribution under the sort of elevated CO2 conditions occurring with leakages from geological storages and future ocean acidification scenarios, may partly be determined by quite subtle physiological differentiation.


Assuntos
Dióxido de Carbono/análise , Ecossistema , Ouriços-do-Mar/fisiologia , Poluentes Químicos da Água/análise , Adaptação Fisiológica , Animais , Mudança Climática , Fenômenos Geológicos , Concentração de Íons de Hidrogênio , Itália , Água do Mar/química
18.
J Nucl Med ; 53(7): 1102-9, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22661534

RESUMO

UNLABELLED: Noninvasive methods are needed to explore the heterogeneous tumor microenvironment and its modulation by therapy. Hybrid PET/MRI systems are being developed for small-animal and clinical use. The advantage of these integrated systems depends on their ability to provide MR images that are spatially coincident with simultaneously acquired PET images, allowing combined functional MRI and PET studies of intratissue heterogeneity. Although much effort has been devoted to developing this new technology, the issue of quantitative and spatial fidelity of PET images from hybrid PET/MRI systems to the tissues imaged has received little attention. Here, we evaluated the ability of a first-generation, small-animal MRI-compatible PET scanner to accurately depict heterogeneous patterns of radiotracer uptake in tumors. METHODS: Quantitative imaging characteristics of the MRI-compatible PET (PET/MRI) scanner were evaluated with phantoms using calibration coefficients derived from a mouse-sized linearity phantom. PET performance was compared with a commercial small-animal PET system and autoradiography in tumor-bearing mice. Pixel and structure-based similarity metrics were used to evaluate image concordance among modalities. Feasibility of simultaneous PET/MRI functional imaging of tumors was explored by following (64)Cu-labeled antibody uptake in relation to diffusion MRI using cooccurrence matrix analysis. RESULTS: The PET/MRI scanner showed stable and linear response. Activity concentration recovery values (measured and true activity concentration) calculated for 4-mm-diameter rods within linearity and uniform activity rod phantoms were near unity (0.97 ± 0.06 and 1.03 ± 0.03, respectively). Intratumoral uptake patterns for both (18)F-FDG and a (64)Cu-antibody acquired using the PET/MRI scanner and small-animal PET were highly correlated with autoradiography (r > 0.99) and with each other (r = 0.97 ± 0.01). On the basis of these data, we performed a preliminary study comparing diffusion MRI and radiolabeled antibody uptake patterns over time and visualized movement of antibodies from the vascular space into the tumor mass. CONCLUSION: The MRI-compatible PET scanner provided tumor images that were quantitatively accurate and spatially concordant with autoradiography and the small-animal PET examination. Cooccurrence matrix approaches enabled effective analysis of multimodal image sets. These observations confirm the ability of the current simultaneous PET/MRI system to provide accurate observations of intratumoral function and serve as a benchmark for future evaluations of hybrid instrumentation.


Assuntos
Imagem por Ressonância Magnética/instrumentação , Imagem por Ressonância Magnética/métodos , Neoplasias/diagnóstico por imagem , Neoplasias/patologia , Tomografia por Emissão de Pósitrons/instrumentação , Tomografia por Emissão de Pósitrons/métodos , Algoritmos , Animais , Anticorpos , Autorradiografia , Calibragem , Radioisótopos de Cobre , Fluordesoxiglucose F18 , Processamento de Imagem Assistida por Computador , Camundongos , Camundongos Endogâmicos C57BL , Imagens de Fantasmas , Compostos Radiofarmacêuticos , Reprodutibilidade dos Testes
19.
Biomaterials ; 32(29): 7209-16, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21742374

RESUMO

In a number of literature reports iron oxide nanoparticles have been investigated for use in imaging atherosclerotic plaques and found to accumulate in plaques via uptake by macrophages, which are critical in the process of atheroma initiation, propagation, and rupture. However, the uptake of these agents is non-specific; thus the labeling efficiency for plaques in vivo is not ideal. We have developed targeted agents to improve the efficiency for labeling macrophage-laden plaques. These probes are based on iron oxide nanoparticles coated with dextran sulfate, a ligand of macrophage scavenger receptor type A (SR-A). We have sulfated dextran-coated iron oxide nanoparticles (DIO) with sulfur trioxide, thereby targeting our nanoparticle imaging agents to SR-A. The sulfated DIO (SDIO) remained mono-dispersed and had an average hydrodynamic diameter of 62 nm, an r(1) relaxivity of 18.1 mM(-1) s(-1), and an r(2) relaxivity of 95.8 mM(-1) s(-1) (37 °C, 1.4 T). Cell studies confirmed that these nanoparticles were nontoxic and specifically targeted to macrophages. In vivo MRI after intravenous injection of the contrast agent into an atherosclerotic mouse injury model showed substantial signal loss on the injured carotid at 4 and 24 h post-injection of SDIO. No discernable signal decrease was seen at the control carotid and only mild signal loss was observed for the injured carotid post-injection of non-sulfated DIO, indicating preferential uptake of the SDIO particles at the site of atherosclerotic plaque. These results indicate that SDIO can facilitate MRI detection and diagnosis of vulnerable plaques in atherosclerosis.


Assuntos
Compostos Férricos/química , Imagem por Ressonância Magnética/métodos , Nanopartículas Metálicas/química , Placa Aterosclerótica/patologia , Animais , Apolipoproteínas E/genética , Materiais Biocompatíveis/química , Materiais Biocompatíveis/metabolismo , Linhagem Celular , Humanos , Teste de Materiais , Camundongos , Camundongos Knockout , Estrutura Molecular , Tamanho da Partícula
20.
Cytopathology ; 22(3): 179-83, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20636404

RESUMO

OBJECTIVE: The cytological examination of pleural effusions is an important investigation in the diagnosis of malignancy. Maximizing the chances of identifying malignant effusions is therefore desirable. Recent Royal College of Pathologists guidelines, based on the British Society for Clinical Cytology codes of practice, have suggested that a minimum of 20 ml of pleural fluid is required for diagnostic purposes. METHODS & RESULTS: We examined 2155 pleural fluids received over a 6-year period in order to define a minimum required volume for adequacy. By examining the plateau phase of a graph of threshold volumes for initial samples received for each patient (n =1584) we determine that a minimum fluid volume of 25 ml is required and that more than 50 ml does not improve sensitivity. CONCLUSION: Between 25 and 50 ml of fluid are required for the adequate assessment of pleural effusions for malignancy.


Assuntos
Derrame Pleural Maligno/diagnóstico , Derrame Pleural Maligno/patologia , Biópsia , Humanos , Auditoria Médica , Reprodutibilidade dos Testes
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