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1.
J Zoo Wildl Med ; 50(4): 891-896, 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31926520

RESUMO

Clinical assessment of renal function in avian species often involves the measurement of plasma uric acid and blood urea nitrogen, relatively insensitive markers of renal dysfunction and dehydration. In mammals, endogenous creatinine is widely used as an indicator of renal glomerular dysfunction. However, avian species produce primarily creatine. Here, renal creatine, 99mTc99-DTPA (diethylenepentaacetic acid, DTPA) and 99mTc-MAG3 (mercaptoacetyl triglycine, MAG3) renal clearances are characterized in the pigeon avian model by infusing DTPA with inulin and creatine with each tracer and examining the slope of their blood disappearance curves. Clearance curves for inulin and DTPA were parallel, suggesting DTPA is cleared by renal filtration. MAG3 clearance (slope: -2.74 × 105, r2 = 0.97) had a slope almost 10-fold steeper than for DTPA (slope: -6.29 × 104, r2 = 0.90), and orders of magnitude steeper than for creatine (slope: -1.4, r2 = 1.0). These results suggest that DTPA is cleared by glomerular filtration like inulin, while MAG3 is filtered and actively excreted in a manner similar to mammals. In contrast, creatine is filtered and resorbed, has a larger volume of distribution (Vd), or exhibits a greater blood protein binding, making it more complex as a renal marker, when compared with creatinine handling in mammals. The two radiotracers can be readily adapted for use in birds, inviting both qualitative and semiquantitative functional evaluation of avian renal function for research and clinical purposes. The elimination of creatine appears to be more complex requiring further study.


Assuntos
Columbidae/metabolismo , Creatina/metabolismo , Rim/metabolismo , Oligopeptídeos/metabolismo , Ácido Pentético/farmacocinética , Polietilenoimina/análogos & derivados , Animais , Meios de Contraste/farmacocinética , Polietilenoimina/farmacocinética
2.
World Neurosurg ; 133: e434-e442, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31525478

RESUMO

OBJECTIVE: To assess the association of degree of contrast stasis in intracranial aneurysms (IAs) immediately after Pipeline embolization device (PED; Medtronic, Dublin, Ireland) deployment with 6- and 12-month angiographic occlusion rates. METHODS: This retrospective cohort study included consecutive patients undergoing PED deployment for saccular IA treatment at a large-volume cerebrovascular center over a 4-year 9-month period. Angiographic images obtained immediately after PED deployment were graded according to amount of intra-aneurysmal contrast flow during the late venous phase: 0 = no stasis; 1 = <50% contrast stasis; 2 = 50%-75% stasis; and 3 = >75%-99% stasis. Follow-up occlusion rates were determined by digital subtraction angiography, computed tomographic angiography, or magnetic resonance angiography. RESULTS: The study included 119 patients in whom 182 PEDs were deployed to treat 141 aneurysms. A single PED was deployed in 105 (74.5%) aneurysms. The internal carotid artery was the commonest aneurysm site (119 [85%]). Fifty-two (36.9%) aneurysms were grade 0; 33 (23.4%) were grade 1; 46 (32.6%) were grade 2; and 10 (7.1%) were grade 3 immediately post-treatment. A 6-month follow-up angiogram available for 101 aneurysms showed complete occlusion (no flow into the aneurysm) in 74 (73.3%) aneurysms. A 12-month follow-up study available for 132 aneurysms showed complete occlusion in 79.5%. At last follow-up, occlusion rates were not significantly different for different contrast stasis grades (P = 0.60). Mean angiographic follow up for all IAs was 23v±v17.7 months. IA size, sex, age, and smoking were not significant predictors of occlusion. CONCLUSIONS: The degree of aneurysm contrast stasis immediately after PED deployment is not statistically associated with 6- and 12-month angiographic occlusion rates.


Assuntos
Embolização Terapêutica/instrumentação , Hemorreologia , Aneurisma Intracraniano/terapia , Stents , Adulto , Idoso , Angiografia Digital , Angiografia Cerebral , Meios de Contraste/farmacocinética , Embolização Terapêutica/métodos , Feminino , Seguimentos , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Método Simples-Cego , Trombose/etiologia , Resultado do Tratamento
3.
Eur Radiol ; 30(1): 1-10, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31278580

RESUMO

OBJECTIVES: Various imaging methods have been evaluated regarding non-invasive differentiation of renal cell carcinoma (RCC) subtypes. Dual-energy computed tomography (DECT) allows iodine concentration (IC) analysis as a correlate of tissue perfusion. Microvascular density (MVD) in histopathology specimens is evaluated to determine intratumoral vascularization. The objective of this study was to assess the potential of IC and MVD regarding the differentiation between papillary and clear cell RCC and between well- and dedifferentiated tumors. Further, we aimed to investigate a possible correlation between these parameters. METHODS: DECT imaging series of 53 patients with clear cell RCC (ccRCC) and 15 with papillary RCC (pRCC) were analyzed regarding IC. Histology samples were stained using CD31/CD34 monoclonal antibodies; MVD was evaluated digitally. Statistical analysis included performance of Mann-Whitney U test, ROC analysis, and Spearman rank correlation. RESULTS: Analysis of IC demonstrated significant differences between ccRCC and pRCC (p < 0.001). A cutoff value of ≤ 3.1 mg/ml at IC analysis allowed identification of pRCC with an accuracy of 86.8%. Within the ccRCC subgroup, G1/G2 tumors could significantly be differentiated from G3/G4 carcinomas (p = 0.045). A significant positive correlation between IC and MVD could be determined for the entire RCC cohort and the ccRCC subgroup. Limitations include the small percentage of pRCCs. CONCLUSIONS: IC analysis is a useful method to differentiate pRCC from ccRCC. The significant positive correlation between IC and MVD indicates valid representation of tumor perfusion by DECT. KEY POINTS: • Analysis of iodine concentration using DECT imaging could reliably distinguish papillary from clear cell subtypes of renal cell cancer (RCC). • A cutoff value of 3.1 mg/ml allowed a distinction between papillary and clear cell RCCs with an accuracy of 86.8%. • The positive correlation with microvascular density in tumor specimens indicates correct display of perfusion by iodine concentration analysis.


Assuntos
Carcinoma Papilar/patologia , Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Papilar/irrigação sanguínea , Carcinoma Papilar/diagnóstico por imagem , Carcinoma de Células Renais/irrigação sanguínea , Carcinoma de Células Renais/diagnóstico por imagem , Transformação Celular Neoplásica/patologia , Meios de Contraste/farmacocinética , Feminino , Humanos , Iodo/farmacocinética , Neoplasias Renais/irrigação sanguínea , Neoplasias Renais/diagnóstico por imagem , Masculino , Microvasos/diagnóstico por imagem , Microvasos/patologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Estatísticas não Paramétricas , Tomografia Computadorizada por Raios X/métodos , Carga Tumoral
4.
Eur Radiol ; 30(1): 640-651, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31407030

RESUMO

OBJECTIVES: The aim of this study was to investigate the prevalence and prognostic value of late gadolinium enhancement (LGE), as assessed by cardiovascular magnetic resonance (CMR) imaging, in patients with aortic stenosis. METHODS AND RESULTS: A systematic search of PubMed and EMBASE was performed, and observational cohort studies that analysed the prevalence of LGE and its relation to clinical outcomes in patients with aortic stenosis were included. Odds ratios were used to measure an effect of the presence of LGE on both all-cause and cardiovascular mortality. Nineteen studies were retrieved, accounting for 2032 patients (mean age 69.8 years, mean follow-up 2.8 years). We found that LGE is highly prevalent in aortic stenosis, affecting half of all patients (49.6%), with a non-infarct pattern being the most frequent type (63.6%). The estimated extent of focal fibrosis, expressed in % of LV mass, was equal to 3.83 (95% CI [2.14, 5.52], p < 0.0001). The meta-analysis showed that the presence of LGE was associated with increased all-cause (pooled OR [95% CI] = 3.26 [1.72, 6.18], p = 0.0003) and cardiovascular mortality (pooled OR [95% CI] = 2.89 [1.90, 4.38], p < 0.0001). CONCLUSIONS: LGE by CMR is highly prevalent in aortic stenosis patients and exhibits a substantial value in all-cause and cardiovascular mortality prediction. These results suggest a potential role of LGE in aortic stenosis patient risk stratification. KEY POINTS: • Up to the half of aortic stenosis patients are affected by myocardial focal fibrosis. • Sixty-four percent of focal fibrosis detected by LGE-CMR is non-infarct type. • The presence of focal fibrosis triples all-cause and cardiovascular mortality.


Assuntos
Estenose da Valva Aórtica/diagnóstico por imagem , Meios de Contraste/farmacocinética , Gadolínio/farmacocinética , Aumento da Imagem/métodos , Imagem por Ressonância Magnética/métodos , Idoso , Aorta/diagnóstico por imagem , Estenose da Valva Aórtica/patologia , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Observacionais como Assunto , Prevalência , Prognóstico
5.
Cancer Imaging ; 19(1): 75, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31730491

RESUMO

BACKGROUND: To evaluate the predictive value of the lipiodol retention pattern for local progression of HCC with a complete response (CR) on CT according to mRECIST criteria after a first session of conventional chemoembolization (cTACE). METHODS: From January 2014 to May 2016 all consecutive patients undergoing a first cTACE session for HCC were identified. Inclusion criteria were the presence of ≤3 HCCs and available pre- and post-cTACE CT. Tumor response was classified according to mRECIST criteria. The analysis focused on tumors with a CR. The lipiodol retention pattern in these tumors was classified as complete (C-Lip, covering the entire tumor volume), or incomplete (I-Lip). Local progression was defined as the reappearance of areas of enhancement on arterial-phase images with washout on portal/delayed phase images within 2 cm from treated tumors on follow-up CT. RESULTS: The final population included 50 patients with 82 HCCs. A total of 46 (56%) HCCs were classified with a CR, including 16 (35%) with I-Lip, and 30 (65%) with C-Lip. After a median follow-up of 14 months (3.2-35.9 months), 15/16 (94%) and 10/30 (30%) of I-Lip and C-Lip HCCs showed local progression on CT, respectively (p < 0.001), with no significant difference in the time to progression (mean 11.1 ± 2 vs. 13.4 ± 3 months for I-Lip and C-Lip, respectively p = 0.51). CONCLUSIONS: HCCs with incomplete lipiodol retention after a first cTACE session have a high risk of local progression even when there is a CR according to mRECIST, and should be considered to be incompletely treated.


Assuntos
Carcinoma Hepatocelular/diagnóstico por imagem , Quimioembolização Terapêutica/métodos , Meios de Contraste/farmacocinética , Óleo Etiodado/farmacocinética , Neoplasias Hepáticas/diagnóstico por imagem , Adulto , Idoso , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/terapia , Progressão da Doença , Feminino , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X/métodos , Tomografia Computadorizada por Raios X/normas , Resultado do Tratamento
6.
Curr Med Sci ; 39(5): 825-830, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31612403

RESUMO

To explore the feasibility and superiority of iodine delivery rate (IDR) and tube voltage determined by patients' body mass index (BMI) in coronary CT angiography (CCTA), a total of 1567 patients undertaking CCTA during Feb. and Dec. 2016 were enrolled and divided into two groups. In the control group, the IDR and tube voltage were fixed, while in the experimental group, the IDR and tube voltage were determined by patients' BMI. The volume of iodinated contrast media (ICM), extravasation rate, extravasation volume, extravasation recovery interval, incidence rate of adverse reactions, effective dose (ED) and image quality of the two groups were compared. The experiments demonstrated that the ICM volume, extravasation rate, extravasation volume, extravasation recovery interval, incidence of adverse reactions and ED were lower or shorter in the experimental group than in the control group, and the differences were statistically significant (all P<0.05). However, there were no significant differences in the mean CT value, image noise, signal to noise ratio and contrast to noise ratio between the two groups (all P<0.05), which were consistent with the diagnosticians' subjective evaluation outcomes. Our findings suggested that in CCTA, it is feasible to determine the IDR and tube voltage based on patients' BMI; low tube voltage and IDR are superior to the fixed tube voltage and IDR and are worthy of clinical promotion.


Assuntos
Angiografia por Tomografia Computadorizada/métodos , Meios de Contraste/farmacocinética , Angiografia Coronária/métodos , Doença da Artéria Coronariana/diagnóstico por imagem , Extravasamento de Materiais Terapêuticos e Diagnósticos/diagnóstico por imagem , Iodo/farmacocinética , Índice de Massa Corporal , Doença da Artéria Coronariana/sangue , Extravasamento de Materiais Terapêuticos e Diagnósticos/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão Sinal-Ruído
7.
Eur J Radiol ; 120: 108698, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31600640

RESUMO

PURPOSE: The aim of the study is to explore the patient's and scan's parameters that affect the iodine concentration in the abdomen using dual energy computed tomography (DECT) in an oncologic population. METHOD: This is a retrospective study with consecutive patients with different cancers who underwent a single-source DECT (ssDECT) examinations at our institution between years 2015 and 2017. On axial IODINE images, the radiologist manually drew a circular ROI along the inner contour of the aorta. Mean iodine concentration and ROI areas were recorded. Body mass index for every patient was recorded. Descriptive statistics were summarized for iodine concentration and patient/scan characteristics. Linear regression was used to examine associations between iodine concentration in aorta and studied characteristics. Statistical significance was set at a p value < 0.05. RESULTS: The univariate analysis, showed a statistically significant association between iodine concentration within the aorta and the area of ROI (Estimated Coefficient ß: -0.013), the rate of injection (Estimated Coefficient ß: 2.09), the acquisition time (Estimated Coefficient ß: -0.195). In multivariable analysis iodine concentration in the aorta increased with higher rate of injection (4 ml/sec), smaller ROI area and lower BMI. CONCLUSION: Our results showed how iodine concentration is highly dependent on some intrinsic and extrinsic parameters of the examination. These parameters should be taken into account since lower concentration of iodine decrease contrast-to-noise ratio, and in longitudinal follow up studies, they would affect iodine quantitive assessments in cancer patients with frequent chemotherapy-induced variations in BMI and cardiac function.


Assuntos
Meios de Contraste/farmacocinética , Iodo/farmacocinética , Neoplasias/diagnóstico por imagem , Intensificação de Imagem Radiográfica/métodos , Imagem Radiográfica a Partir de Emissão de Duplo Fóton/métodos , Tomografia Computadorizada por Raios X/métodos , Adulto , Aorta/metabolismo , Índice de Massa Corporal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
8.
Chem Biodivers ; 16(11): e1900322, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31544357

RESUMO

The synthesis of poly[N,N-bis(3-aminopropyl)glycine] (PAPGly) dendrons Gd-based contrast agents (GdCAs) via an orthogonal protection of the different functional groups and an activation/coupling strategy wherein a specific number of synthetic steps add a generation to the existing dendron has been described. The aim of this protocol is to build up two different generations of dendrons (G-0 or dendron's core, and G-1) with peripheral NH2 groups to conjugate a 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid (DO3A) derivative and afterwards to chelate with Gd3+ paramagnetic ions. These complexes, which have a well-defined molecular weight, are of relevance to MRI as an attempt to gain higher 1 H relaxivity by slowing down the rotation of molecule compared to monomeric Gd(III) complexes used as contrast agents and to increase the number of paramagnetic centers present in one molecular structure. From the study of their water 1 H longitudinal relaxation rate at different magnetic fields (NMRD, Nuclear Magnetic Relaxation Dispersion) and by evaluating the variable temperature 17 O-NMR data we determined the parameters characterizing the water exchange rate and the rotational correlation time of each complex, both affecting 1 H relaxivity. Furthermore, these two novel PAPGly GdCAs were objects of i) an in vivo study to determine their biodistributions in healthy C57 mice at several time points, and ii) the Dynamic Contrast-Enhanced MRI (DCE-MRI) approach to assess their contrast efficiency measured in the tumor region of C57BL/6 mice transplanted subcutaneously with B16-F10 melanoma cells. The aim of the comparison of these two dendrons GdCAs, having different molecular weights (MW), is to understand how MW and relaxivity may influence the contrast enhancement capabilities in vivo at low magnetic field (1 T). Significant contrast enhancement was observed in several organs (vessel, spleen and liver), already at 5 min post-injection, for the investigated CAs. Moreover, these CAs induced a marked contrast enhancement in the tumor region, thanks to the enhanced permeability retention effect of those macromolecular structures.


Assuntos
Meios de Contraste/química , Gadolínio/química , Melanoma/química , Compostos Organometálicos/química , Animais , Meios de Contraste/síntese química , Meios de Contraste/farmacocinética , Gadolínio/farmacocinética , Humanos , Imagem por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Masculino , Melanoma/diagnóstico por imagem , Camundongos , Camundongos Endogâmicos C57BL , Estrutura Molecular , Neoplasias Experimentais/química , Neoplasias Experimentais/diagnóstico por imagem , Compostos Organometálicos/síntese química , Compostos Organometálicos/farmacocinética , Distribuição Tecidual
9.
Nanoscale ; 11(34): 15958-15970, 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31418432

RESUMO

Oral drug delivery systems (ODDSs) have attracted considerable attention in relation to orthotopic colon cancer therapy due to certain popular advantages. Unfortunately, their clinical applications are generally limited by the side-effects caused by systemic drug exposure and poor real-time monitoring capabilities. Inspired by the characteristics of pH changes of the gastrointestinal tract (GIT) and specific enzymes secreted by the colonic microflora, we anchored polyacrylic acid (PAA) and chitosan (CS) on Gd3+-doped mesoporous hydroxyapatite nanoparticles (Gd-MHAp NPs) to realize programmed drug release and magnetic resonance imaging (MRI) at the tumor sites. In particular, the grafted PAA, as a pH-responsive switch, could effect controlled drug release in the colon. Further, CS is functionalized as the enzyme-sensitive moiety, which could be degraded by ß-glycosidase in the colon. Gadolinium is a paramagnetic lanthanide element used in chelates, working as a contrast medium agent for an MRI system. Interestingly, after oral administration, CS and PAA could protect the drug-loaded nanoparticles (NPs) against variable physiological conditions in the GIT, allowing the drug to reach the colon tumor sites, preventing premature drug release. Enhanced drug concentrations at the colon tumor sites were achieved via this programmed drug release, which subsequently ameliorated the therapeutic effect. In addition, encapsulating both chemotherapeutic (5-fluorouracil, 5-FU) and targeted therapy drug (gefitinib, Gef) within Gd-MHAp NPs produced a synergistic therapeutic effect. In summary, this study demonstrated that such a novel drug system (Gd-MHAp/5-FU/Gef/CS/PAA NPs) could protect, transport, and program drug release locally within the colonic environment; further, this system exhibited a worthwhile therapeutic effect, providing a promising novel treatment strategy for orthotopic colon cancer.


Assuntos
Neoplasias do Colo , Meios de Contraste , Fluoruracila , Gadolínio , Gefitinibe , Imagem por Ressonância Magnética , Nanopartículas , Resinas Acrílicas/química , Resinas Acrílicas/farmacocinética , Resinas Acrílicas/farmacologia , Administração Oral , Animais , Quitosana/química , Quitosana/farmacocinética , Quitosana/farmacologia , Neoplasias do Colo/diagnóstico por imagem , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/metabolismo , Meios de Contraste/química , Meios de Contraste/farmacocinética , Meios de Contraste/farmacologia , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/farmacologia , Durapatita/química , Durapatita/farmacocinética , Durapatita/farmacologia , Fluoruracila/química , Fluoruracila/farmacocinética , Fluoruracila/farmacologia , Gadolínio/química , Gadolínio/farmacocinética , Gadolínio/farmacologia , Gefitinibe/química , Gefitinibe/farmacocinética , Gefitinibe/farmacologia , Células HT29 , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/química , Nanopartículas/uso terapêutico
10.
J Colloid Interface Sci ; 556: 128-139, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31437658

RESUMO

Magnetic drug delivery system is one of the most important strategies for cancer diagnosis and treatment. In this study, a novel theranostic system was fabricated based on cyclodextrin nanosponge (CDNS) polymer anchored on the surface of Magnetite nanoparticles (Fe3O4/CDNS NPs) which was then decorated with folic acid (FA) as a targeting agent (Fe3O4/CDNS-FA). Curcumin (CUR), a hydrophobic model drug, was next loaded into the cyclodextrin cavity and polymeric matrix of CDNS (Fe3O4/CDNS-FA@CUR). The system was fully characterized. The in vitro release study revealed pH-sensitive behavior. Cytotoxicity assays indicated a negligible toxicity for CUR free Fe3O4/CDNS-FA NPs against both of M109 cancerous cells and MCF 10A normal cells. CUR-loaded Fe3O4/CDNS-FA NPs exhibited higher toxicity against M109 cancerous cells than MCF 10A normal cells (p < 0.05). Fe3O4/CDNS-FA@CUR NPs resulted in much more cell viability on normal cells than pure CUR (p < 0.05). Moreover, blood compatibility study showed minor hemolytic activity. In vitro MRI studies illustrated negative signal increase in cells affirming acceptable diagnostic ability of the nanocarrier. The T2 MR signal intensity for Fe3O4/CDNS-FA@CUR NPs in M109 cells was around 2-fold higher than that of MCF 10A cells. This implies two times higher selective cellular uptake of the Fe3O4/CDNS-FA@CUR NPs into M109 cell compared to MCF 10A. The multifunctional nanocarrier could be considered as promising candidate for cancer theranostics because of the smart drug release, selective cytotoxicity, suitable hemocompatibility, and proper T2 MRI contrast efficiency.


Assuntos
Materiais Revestidos Biocompatíveis , Meios de Contraste , Curcumina , Sistemas de Liberação de Medicamentos , Ácido Fólico , Imagem por Ressonância Magnética , Nanopartículas de Magnetita , Neoplasias , Linhagem Celular Tumoral , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacocinética , Materiais Revestidos Biocompatíveis/farmacologia , Meios de Contraste/química , Meios de Contraste/farmacocinética , Meios de Contraste/farmacologia , Curcumina/química , Curcumina/farmacocinética , Curcumina/farmacologia , Ácido Fólico/química , Ácido Fólico/farmacocinética , Ácido Fólico/farmacologia , Humanos , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/uso terapêutico , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico
11.
Eur J Radiol ; 118: 51-57, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31439258

RESUMO

PURPOSE: To test the potential impact of pharmacokinetic parameters, derived from DCE-MRI analysis, on the diagnostic performance of PI-RADSv.2 classification in prostate lesions characterization. METHOD: Among patients who underwent multiparametric prostate MRI (mpMRI) (January 2016-March 2018) followed by histological evaluation (targeted biopsies/prostatectomy), 103 men were retrospectively selected. For each patient the index lesion was identified and pharmacokinetic parameters (Ktrans, Kep, Ve, Vp) were assessed. MRI diagnostic performance in the detection of significant tumors [Gleason Score (GS)≥7] was assessed, considering PI-RADS≥3 as positive. RESULTS: GS ≥ 7 (n = 59) showed higher Ktrans (p < 0.01) and Kep (p = 0.01) compared to GS < 7. At ROC curve analysis, a Ktrans cut-off of 191 × 10-3/min was identified to predict the presence of GS ≥ 7 (AUC:0.75; sensitivity:95%; specificity:61%). Sensitivity and PPV of mpMRI using PI-RADSv.2 were 98% and 61%. Reclassifying PI-RADS≥3 lesions according to Ktrans cut-off, 22 false positives were shifted to true negatives with 3 false negative findings; PPV raised to 79%. Appling Ktrans cut-off to PI-RADS 3 lesions of peripheral zone (n = 18), 12 true negatives, 4 true positives, 2 false positives were identified. CONCLUSIONS: Despite its high sensitivity prostate mpMRI generates many false positive cases: Ktrans in addition to PIRADS v.2 seems to improve MRI-PPV and may help in avoiding redundant biopsies.


Assuntos
Meios de Contraste/farmacocinética , Aumento da Imagem/métodos , Imagem por Ressonância Magnética/métodos , Neoplasias da Próstata/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Estudos de Avaliação como Assunto , Reações Falso-Positivas , Humanos , Masculino , Pessoa de Meia-Idade , Próstata/diagnóstico por imagem , Próstata/patologia , Neoplasias da Próstata/patologia , Curva ROC , Sistemas de Informação em Radiologia , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade
12.
ACS Appl Mater Interfaces ; 11(37): 33650-33658, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31448891

RESUMO

Spectral computed tomography (CT) imaging as a novel imaging technique shows promising prospects in the accurate diagnosis of various diseases. However, clinically iodinated contrast agents suffer from poor signal-to-noise ratio, and emerging heavy-metal-based CT contrast agents arouse great biosafety concern. Herein, we show the fabrication of rhenium sulfide (ReS2) nanoparticles, a clinic radiotherapy sensitizer, as a biosafe spectral CT contrast agent for the gastrointestinal tract imaging and tumor theranostics in vivo by teaching old drugs new tricks. The ReS2 nanoparticles were fabricated in a one-pot facile method at room temperature, and exhibited sub-10 nm size, favorable monodispersity, admirable aqueous solubility, and strong X-ray attenuation capability. More importantly, the proposed nanoparticles possess an outstanding spectral CT imaging ability and undoubted biosafety as a clinic therapeutic agent. Besides, the ReS2 nanoparticles possess appealing photothermal performance due to their intense near-infrared absorption. The proposed nano-agent not only guarantees obvious contrast enhancement in gastrointestinal tract spectral CT imaging in vivo, but also allows effective CT imaging-guided tumor photothermal therapy. The proposed "teaching old drugs new tricks" strategy shortens the time and cuts the cost required for clinical application of nano-agents based on existing clinical toxicology testing and trial results, and lays down a low-cost, time-saving, and energy-saving method for the development of multifunctional nano-agents toward clinical applications.


Assuntos
Meios de Contraste , Trato Gastrointestinal/diagnóstico por imagem , Hipertermia Induzida , Nanopartículas , Neoplasias , Fototerapia , Rênio , Sulfetos , Nanomedicina Teranóstica , Tomografia Computadorizada por Raios X , Animais , Linhagem Celular Tumoral , Meios de Contraste/química , Meios de Contraste/farmacocinética , Meios de Contraste/farmacologia , Camundongos , Nanopartículas/química , Nanopartículas/uso terapêutico , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Rênio/química , Rênio/farmacocinética , Rênio/farmacologia , Sulfetos/química , Sulfetos/farmacocinética , Sulfetos/farmacologia
13.
Neurology ; 93(6): e611-e623, 2019 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-31285398

RESUMO

OBJECTIVE: Frequent administration of gadolinium-based contrast agents in multiple sclerosis (MS) may increase signal intensity (SI) unenhanced T1-weighted imaging MRI throughout the brain. We evaluated the association between lifetime cumulative doses of gadodiamide administration and increased SI within the dentate nucleus (DN), globus pallidus (GP), and thalamus in patients with early MS. METHODS: A total of 203 patients with MS (107 with baseline and follow-up MRI assessments) and 262 age- and sex-matched controls were included in this retrospective, longitudinal, 3T MRI-reader-blinded study. Patients with MS had disease duration <2 years at baseline and received exclusively gadodiamide at all MRI time points. SI ratio (SIR) to pons and CSF of lateral ventricle volume (CSF-LVV) were assessed. Analysis of covariance and correlation analyses, adjusted for age, sex, and region of interest volume, were used. RESULTS: The mean follow-up time was 55.4 months, and the mean number of gadolinium-based contrast agents administrations was 9.2. At follow-up, 49.3% of patients with MS and no controls showed DN T1 hyperintensity (p < 0.001). The mean SIR of DN (p < 0.001) and of GP (p = 0.005) to pons and the mean SIR of DN, GP, and thalamus to CSF-LVV were higher in patients with MS compared to controls (p < 0.001). SIR of DN to pons was associated with number of gadodiamide doses (p < 0.001). No associations between SIR of DN, GP, and thalamus and clinical and MRI outcomes of disease severity were detected over the follow-up. CONCLUSIONS: DN, GP, and thalamus gadolinium deposition in early MS is associated with lifetime cumulative gadodiamide administration without clinical or radiologic correlates of more aggressive disease.


Assuntos
Encéfalo/metabolismo , Meios de Contraste/farmacocinética , Gadolínio DTPA/farmacocinética , Gadolínio/metabolismo , Esclerose Múltipla/metabolismo , Adulto , Encéfalo/diagnóstico por imagem , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/diagnóstico por imagem , Estudos Retrospectivos
14.
Regul Toxicol Pharmacol ; 107: 104417, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31276731

RESUMO

MB-102 was designed for measurement of real-time glomerular filtration rate (GFR). Previously reported in vitro and in vivo nonclinical studies clearly demonstrated negligible toxicity, resulting in FDA clearance for First-in Human, proof of concept clinical studies. The next tier of safety and toxicity studies are reported herein. MB-102 did not demonstrate any phototoxic potential in a BALB/c 3T3 mouse fibroblast study. Co-administration of MB-102 and iohexol resulted in pharmacokinetic parameters virtually identical to the values observed upon individual administration in beagle dogs. A single dose of MB-102 administered either intravenously (18.6 mg/mL) or perivenously (0.25 mL) was well-tolerated in NZ white rabbits, with no adverse inflammation or irritation. MB-102 did not induce micronuclei in polychromatic erythrocytes for rat bone marrow cells treated up to 450 mg/kg/day, the maximum feasible dose. Two separate optical imaging studies demonstrated that MB-102 distributes rapidly and thoroughly throughout the test subjects, followed by rapid clearance from the body without any preferential localization in any particular tissue or organ, with the exception of the bladder, which is totally consistent with a known GFR agent. In addition, two-week repeat intravenous (once-daily) toxicity and toxicokinetic studies were conducted in rats and beagles, with no MB-102- related effects. Thus, for the studies reported herein, there were no toxicological effects of concern for MB-102.


Assuntos
Corantes Fluorescentes/toxicidade , Pirazinas/toxicidade , Animais , Células 3T3 BALB , Meios de Contraste/farmacocinética , Dermatite Fototóxica , Cães , Interações de Medicamentos , Feminino , Corantes Fluorescentes/farmacocinética , Taxa de Filtração Glomerular , Iohexol/farmacocinética , Masculino , Camundongos , Camundongos Nus , Testes para Micronúcleos , Pirazinas/farmacocinética , Coelhos , Ratos Sprague-Dawley
15.
Br J Radiol ; 92(1103): 20190302, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31271535

RESUMO

OBJECTIVES: To compare a low-dose dynamic contrast-enhanced breast MRI protocol (LITE MRI) to standard-dosage using a dual-dose injection technique. METHODS: 8 females with a total of 10 lesions with imaging features compatible with fibroadenoma were imaged using a dual-dose dynamic contrast-enhanced-MRI (DCE-MRI) technique. After pre-contrast scans, 15% of a standard dose of contrast was administered; approximately 10 min later, the remaining 85% of the standard dose was administered. Enhancement kinetic parameters, conspicuity and signal-to-noise ratio were measured quantitatively. RESULTS: One lesion showed no enhancement in either DCE series. All nine of the enhancing lesions were visualized in both the low-dose and standard-dose images. While the (low-to-standard) ratio of contrast doses was roughly 0.18, this did not match the ratios of kinetic parameters. Lesion conspicuity and enhancement rate were both higher in the low-dose images, with (low-to-standard) ratios 1.5 ± 0.1 and 1.2 ± 0.4, respectively. The upper limit of enhancement (ratio 0.3 ± 0.1) and signal-to-noise ratio (ratio 0.5 ± 0.1) were higher in the standard-dose images, but less than expected based on the ratio of the doses. CONCLUSIONS: This preliminary study demonstrates that LITE MRI has the potential to match standard DCE-MRI in the detection of enhancing lesions. Additionally, LITE MRI may enhance sensitivity to contrast media dynamics. ADVANCES IN KNOWLEDGE: Lower doses of MRI contrast media may be equally effective in the detection of breast lesions, and increase sensitivity to contrast media dynamics. LITE MRI may help increase screening compliance and long-term patient safety.


Assuntos
Neoplasias da Mama/diagnóstico , Fibroadenoma/diagnóstico , Adolescente , Adulto , Meios de Contraste/administração & dosagem , Meios de Contraste/farmacocinética , Relação Dose-Resposta a Droga , Feminino , Gadolínio/administração & dosagem , Gadolínio/farmacocinética , Humanos , Imagem por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Razão Sinal-Ruído , Adulto Jovem
16.
PLoS One ; 14(7): e0217384, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31260447

RESUMO

[18F]T807 is a potent tau protein imaging agent. In order to fulfill the demand from preclinical and clinical studies, we developed an automated one-pot two-step synthesis of this potent tau imaging agent and studied its stability, and dosimetry in mice and monkeys. We also conducted a preliminary study of this imaging agent in humans. Using this one-pot two-step method, the radiochemical yield (RCY) of [18F]T807 was 20.5 ± 6.1% (n = 15) at the end of bombardment (EOB) in a synthesis time of 70±5 min. The chemical and radiochemical purities were >90% and the specific activities were 151 ± 52 GBq/µmol. The quality of [18F]T807 synthesized by this method met the U.S. Pharmacopoeia (USP) criteria. The stability test showed that the [18F]T807 injection was stable at room temperature for up to 4 h after the end of synthesis (EOS). The estimated effective dose of the [18F]T807 injection extrapolated from monkeys was 19 µSv/MBq (n = 2), while the estimated effective doses of the [18F]T807 injection extrapolated from fasted and non-fasted mice were 123 ± 27 (n = 3) and 94 ± 19 (n = 4) µSv/MBq, respectively. This one-pot two-step automated method produced the [18F]T807 injection with high reproducibility and high quality. PET imaging and radiation dosimetry evaluation in mice and Formosan rock monkeys suggested that the [18F]T807 injection synthesized by this method is suitable for use in human PET imaging studies. Thus, this method could fulfill the demand for the [18F]T807 injection in both preclinical and clinical studies of tauopathies, especially for nearby study sites without cyclotrons.


Assuntos
Doença de Alzheimer/diagnóstico por imagem , Carbolinas/síntese química , Meios de Contraste/síntese química , Compostos Radiofarmacêuticos/síntese química , Proteínas tau/química , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Animais , Disponibilidade Biológica , Carbolinas/sangue , Carbolinas/farmacocinética , Meios de Contraste/farmacocinética , Avaliação Pré-Clínica de Medicamentos , Expressão Gênica , Haplorrinos , Humanos , Injeções Intravenosas , Macaca , Masculino , Camundongos , Camundongos Endogâmicos ICR , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons/métodos , Radiometria , Compostos Radiofarmacêuticos/sangue , Compostos Radiofarmacêuticos/farmacocinética , Distribuição Tecidual , Proteínas tau/genética
17.
Int J Pharm ; 568: 118496, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31279053

RESUMO

Magnetic resonance angiography (MRA) requires the use of contrast agents (CAs) to enable accurate diagnosis. There are currently no CAs on the market with appropriate pharmacokinetic (PK) parameters, namely long persistence in the blood, that can be easily used for MRA. We have recently synthesized amphiphilic building blocks loaded with gadolinium (Gd), which self-assemble into Gd-micelles in aqueous media, and have evaluated their potential as a blood-pool contrast agent (BPCA) in vivo. To assess the short and long term PK of Gd-micelles, the blood and organs of the mice were analyzed at t = 30 min, 1, 2, 3 h, 7, 14 and 21 days. Gd-DOTA was used as a control because it is the gold-standard CA for MRA despite its rapid clearance from the blood compartment. Gd-micelles circulated in the blood for more than 3 h postinjection whereas Gd-DOTA was eliminated less than half an hour postinjection. No side effects were observed in the mice up to the end of the study at 21 days and no accumulation of Gd was observed in the brain or bones. The Magnetic Resonance Imaging (MRI) parameters and the results of this in vivo study indicate the true BCPA properties of Gd-micelles and warrant further development.


Assuntos
Meios de Contraste/farmacocinética , Gadolínio/farmacocinética , Compostos Heterocíclicos/farmacocinética , Micelas , Compostos Organometálicos/farmacocinética , Animais , Sobrevivência Celular/efeitos dos fármacos , Meios de Contraste/administração & dosagem , Gadolínio/administração & dosagem , Compostos Heterocíclicos/administração & dosagem , Humanos , Células MCF-7 , Imagem por Ressonância Magnética , Masculino , Camundongos Endogâmicos BALB C , Compostos Organometálicos/administração & dosagem , Distribuição Tecidual
18.
Magn Reson Imaging Clin N Am ; 27(3): 545-561, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31279456

RESUMO

Late gadolinium enhancement (LGE) has become a standard clinical tool to evaluate myocardial fibrosis to define myocardial viability in the context of ischemic myocardial disease. More recently, LGE has also been used to characterize the presence and pattern of fibrosis in nonischemic cardiomyopathies. It yields unique and valuable diagnostic and prognostic insights for myriad nonischemic clinical indications and has become a key part of routine cardiac MR imaging, and a tool to guide treatment. This article reviews the technical aspects of LGE performance and its diagnostic and prognostic implications in nonischemic cardiomyopathy.


Assuntos
Meios de Contraste/farmacocinética , Gadolínio/farmacocinética , Cardiopatias/diagnóstico por imagem , Aumento da Imagem/métodos , Imagem por Ressonância Magnética/métodos , Humanos , Prognóstico , Reprodutibilidade dos Testes
19.
Invest Radiol ; 54(8): 453-463, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31265439

RESUMO

OBJECTIVES: This preclinical study was devised to investigate potential cellular toxicity in human neurons induced by gadolinium-based contrast agents (GBCAs) used for contrast-enhanced magnetic resonance imaging (MRI). Neurons modeling a subset of those in the basal ganglia were tested, because the basal ganglia region is 1 of 2 brain regions that displays the greatest T1-dependent signal hyperintensity changes. METHODS: Eight GBCAs were tested. Dopaminergic neurons modeling a subset of those in the basal ganglia were differentiated from an established human neuroblastoma cell line and exposed to increasing concentrations of each agent for 7 days. The tested dosages ranged from clinically relevant concentrations measured in some autopsy patients who had received repeated injections of contrast for MRI, to higher concentrations to reveal dose-dependent toxicity trends. Cell death, mitochondrial membrane potential, mitochondrial oxidative capacity, and mitochondrial function measured by oxygen consumption were quantified in cells treated with each GBCA or the osmolality control mannitol and compared to untreated cells which served as a negative control. RESULTS: Mannitol caused no change from negative controls in any of the tests, at any concentration tested. For all GBCAs, cell death increased with exposure dose, with toxicity at clinically relevant doses for agents with lower kinetic stability. Reduction of mitochondrial membrane potential and oxidative respiratory function also generally mirrored the agents' structural kinetic stabilities, with greater impairment at lower concentration for the less stable agents. CONCLUSIONS: In human neurons modeling a subset of those in the basal ganglia, these results demonstrate a toxic effect of gadolinium-containing MRI contrast agents on mitochondrial respiratory function and cell viability. Toxicity increases as agent concentration increases and as the kinetic stability of the agent decreases.


Assuntos
Morte Celular/fisiologia , Meios de Contraste/farmacocinética , Gadolínio/farmacocinética , Aumento da Imagem/métodos , Imagem por Ressonância Magnética/métodos , Neurônios/patologia , Feminino , Humanos , Masculino
20.
Eur Radiol ; 29(12): 6539-6549, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31236701

RESUMO

OBJECTIVES: To evaluate the diagnostic value of Lipiodol distribution in angiography and CT to differentiate between hepatocellular carcinoma (HCC) and benign nodules of LI-RADS 3 and 4 lesions observed in MRI of liver cirrhosis. METHODS: This retrospective study included all patients with liver cirrhosis who had diagnosis of LI-RADS 3 or 4 lesions by MRI who underwent a Lipiodol-based angiography and post-interventional unenhanced CT- and liver biopsy. Two independent radiologists evaluated appearance, contrast enhancement, Lipiodol uptake in angiography, and morphological parameters (size, form, and density) of the lesions in unenhanced post-angiography CT. α-Fetoprotein (AFP) levels and pre-existing liver conditions were additionally taken into consideration. Differences between HCC lesions and benign nodules were analyzed. Sensitivity and specificity were calculated. P < 0.05 was considered as statistically significant. RESULTS: Of 60 patients (men, n = 42 [70.0%]; women, 18 [30.0%]; mean age, 61 ± 9.1 years) 36 (60.0%) had HCC and 24 (40.0%) benign nodules. Clear visibility in angiography (sensitivity [se], 100%; specificity [sp], 87.5%) with homogeneous or lacunar Lipiodol enhancement (se, 86.1%; sp, 100%) in consecutive CT can be diagnosed as HCC lesions in cirrhotic liver. Lesion form (p < 0.001), round or oval, and intense contrast (p < 0.001) are minor features which can facilitate the findings. Furthermore, patients with HCC showed a larger lesion size in CT (p = 0.026). CONCLUSION: Clearly detectable lesions in Lipiodol-based angiography and a homogeneous or lacunar enhancement in post-angiographic non-contrast CT allow for differentiation of intrahepatic lesions classified as LI-RADS 3 or 4 into benign vs. malign liver lesions with high sensitivity and specificity in patients with liver cirrhosis. Definite diagnosis may not require an additional biopsy. KEY POINTS: • Combination of clear visibility in Lipiodol-based angiography and homogeneous or lacunar enhancement in following native CT scan is HCC-defining. • In lesions classified with MRI as LI-RADS 3 or 4, evaluation based on Lipiodol angiography and following plain CT performed is highly sensitive and specific for the differentiation between HCC and benign nodules in a cirrhotic liver. • The results lead to an alternative pathway in the diagnosis of HCC in cirrhotic liver without the need of an additional liver biopsy.


Assuntos
Carcinoma Hepatocelular/diagnóstico por imagem , Meios de Contraste/farmacocinética , Óleo Etiodado/farmacocinética , Cirrose Hepática/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico por imagem , Intensificação de Imagem Radiográfica/métodos , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Angiografia/métodos , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/patologia , Feminino , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/patologia , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e Especificidade
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