Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 16 de 16
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
2.
Environ Sci Technol ; 52(14): 7680-7688, 2018 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-29898357

RESUMO

Atmospheric aerosol particles may contain light absorbing (brown carbon, BrC), triplet forming organic compounds that can sustain catalytic radical reactions and thus contribute to oxidative aerosol aging. We quantify UVA induced radical production initiated by imidazole-2-carboxaldehyde (IC), benzophenone (BPh). and 4-benzoylbenzoic acid (BBA) in the presence of the nonabsorbing organics citric acid (CA), shikimic acid (SA), and syringol (Syr) at varying mixing ratios. We observed a maximum HO2 release of 1013 molecules min-1 cm-2 at a mole ratio XBPh < 0.02 for BPh in CA. Mixtures of either IC or BBA with CA resulted in 1011-1012 molecules min-1 cm-2 of HO2 at mole ratios ( XIC and XBBA) between 0.01 and 0.15. HO2 release was affected by relative humidity ( RH) and film thickness suggesting coupled photochemical reaction and diffusion processes. Quantum yields of HO2 formed per absorbed photon for IC, BBA and BPh were between 10-7 and 5 × 10-5. The nonphotoactive organics, Syr and SA, increased HO2 production due to the reaction with the triplet excited species ensuing ketyl radical production. Rate coefficients of the triplet of IC with Syr and SA measured by laser flash photolysis experiments were kSyr = (9.4 ± 0.3) × 108 M-1 s-1 and kSA = (2.7 ± 0.5) × 107 M-1 s-1. A simple kinetic model was used to assess total HO2 and organic radical production in the condensed phase and to upscale to ambient aerosol, indicating that BrC induced radical production may amount to an upper limit of 20 and 200 M day-1 of HO2 and organic radical respectively, which is greater or in the same order of magnitude as the internal radical production from other processes, previously estimated to be around 15 M per day.


Assuntos
Compostos Orgânicos , Aerossóis , Difusão , Cinética , Oxirredução
3.
J Ophthalmol ; 2017: 8984313, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29093970

RESUMO

Purpose: To evaluate the response of intravitreal aflibercept injection (IAI) in eyes with detachment of retinal pigment epithelium (DEP) secondary to nAMD refractory to monthly ranibizumab. Patients and Methods: This is a retrospective, multicenter study. All patients received 3 IAI then treated as needed every 4 weeks for 12 months. During the second year, the eyes were treated with a treat- and-extend regimen. Results: Forty-four eyes were included. Best-corrected visual acuity improved significantly after the loading phase (3.1 ± 6.4 letters) and at 6 months (2.8 ± 6.4 letters), but change was not significant at 1 year and 2 years. The height of the DEP was significantly decreased at 3 months and 6 months, but the difference did not reach statistical difference at 1 and 2 years. Rate of eyes with complete resolution of exudation was 59% after the loading phase and 34.3% at 2 years. Mean interval of anti-VEGF injection was extended from 31 ± 2.6 days to 61 ± 5 days after conversion. Conclusions: Aflibercept intravitreal injection in patients with fibrovascular DEP due to nAMD who respond poorly to monthly ranibizumab led to short-term functional and anatomical improvement. Reduction of intravitreal injection frequency was obtained until 2 years of follow-up.

5.
Invest Radiol ; 45(10): 613-24, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20808234

RESUMO

RATIONALE AND OBJECTIVES: The observed relaxivity of gadolinium-based contrast agents has contributions from the water molecule(s) that bind directly to the gadolinium ion (inner-sphere water), long-lived water molecules and exchangeable protons that make up the second-sphere of coordination, and water molecules that diffuse near the contrast agent (outer-sphere). Inner- and second-sphere relaxivity can both be increased by optimization of the lifetimes of the water molecules and protons in these coordination spheres, the rotational motion of the complex, and the electronic relaxation of the gadolinium ion. We sought to identify new high-relaxivity contrast agents by systematically varying the donor atoms that bind directly to gadolinium to increase inner-sphere relaxivity and concurrently including substituents that influence the second-sphere relaxivity. METHODS: Twenty gadolinium-1,4,7,10-tetraazacyclo-dodecane-N,N',N″,N'″-tetraacetato derivatives were prepared and their relaxivity determined in presence and absence of human serum albumin as a function of temperature and magnetic field. Data was analyzed to extract the underlying molecular parameters influencing relaxivity. Each compound had a common albumin-binding group and an inner-sphere donor set comprising the 4 tertiary amine N atoms from cyclen, an α-substituted acetate oxygen atom, 2 amide oxygen atoms, an inner-sphere water oxygen atom, and a variable donor group. Each amide nitrogen was substituted with different groups to promote hydrogen bonding with second-sphere water molecules. RESULTS: Relativities at 0.47 and 1.4 T, 37°C, in serum albumin ranged from 16.0 to 58.1 mM(-1)s(-1) and from 12.3 to 34.8 mM(-1)s(-1), respectively. The reduction of inner-sphere water exchange typical of amide donor groups could be offset by incorporating a phosphonate or phenolate oxygen atom donor in the first coordination sphere, resulting in higher relaxivity. Amide nitrogen substitution with pendant phosphonate or carboxylate groups increased relaxivity by as much as 88% compared with the N-methyl amide analog. Second-sphere relaxivity contributed as much as 24 and 14 mM(-1)s(-1) at 0.47 and 1.4 T, respectively. CONCLUSIONS: Water/proton exchange dynamics in the inner- and second-coordination sphere can be predictably tuned by choice of donor atoms and second-sphere substituents, resulting in high-relaxivity agents.


Assuntos
Albuminas/química , Meios de Contraste/química , Gadolínio/química , Imagem por Ressonância Magnética/métodos , Prótons , Albuminas/metabolismo , Fenômenos Químicos , Meios de Contraste/metabolismo , Gadolínio/sangue , Gadolínio/metabolismo , Humanos , Espectroscopia de Ressonância Magnética , Ligação Proteica , Água/química
6.
Invest Radiol ; 45(10): 600-12, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20808235

RESUMO

RATIONALE AND OBJECTIVES: The donor atoms that bind to gadolinium in contrast agents influence inner-sphere water exchange and electronic relaxation, both of which determine observed relaxivity. The effect of these molecular parameters on relaxivity is greatest when the contrast agent is protein bound. We sought to determine an optimal donor atom set to yield high relaxivity compounds. METHODS: A total of 38 gadolinium-1,4,7,10-tetraazacyclo-dodecane-N,N',N'',N'''-tetraacetato derivatives were prepared and relaxivity was determined in the presence and absence of human serum albumin as a function of temperature and magnetic field. Each compound had a common albumin-binding group and differed only by substitution of different donor groups at one of the macrocycle nitrogens. Oxygen-17 isotope relaxometry at 7.05 T was performed to estimate water exchange rates. RESULTS: Changing a single donor atom resulted in changes in water exchange rates ranging across 3 orders of magnitude. Donor groups increased water exchange rate in the order: phosphonate ∼ phenolate > α-substituted acetate > acetate > hydroxamate ∼ sulfonamide > amide ∼ pyridyl ∼ imidazole. Relaxivites at 0.47 and 1.4 T, 37°C, ranged from 12.3 to 55.6 mM(-1)s(-1) and from 8.3 to 32.6 mM(-1)s(-1) respectively. Optimal relaxivities were observed when the donor group was an α-substituted acetate. Electronic relaxation was slowest for the acetate derivatives as well. CONCLUSIONS: Water exchange dynamics and relaxivity can be predictably tuned by choice of donor atoms.


Assuntos
Albuminas/química , Meios de Contraste/química , Gadolínio/sangue , Imagem por Ressonância Magnética/métodos , Meios de Contraste/metabolismo , Gadolínio/química , Humanos , Cinética , Imagem por Ressonância Magnética/instrumentação , Ligação Proteica
9.
Am J Ophthalmol ; 143(1): 68-76, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17188042

RESUMO

PURPOSE: To compare the results of limited macular translocation and photodynamic therapy (PDT) in subfoveal choroidal neovascularization (CNV) attributable to pathologic myopia with a 24-month follow-up. DESIGN: Retrospective analysis of nonrandomized interventional clinical study. METHODS: Retrospective review of 66 consecutive patients: 34 myopic eyes with subfoveal neovascularization treated by PDT and 32 operated on with the translocation technique. Translocation was considered principally when the lesion size was adequate (nasal inferior margin of the membrane less than half a disk diameter away from the center of the fovea) with duration of symptoms of less than four months. Main outcome measure was the postoperative change in visual acuity. RESULTS: In the translocation group, mean gain in visual acuity was greater than in the PDT group (+2.8 lines and -1.8 line, respectively, P = .001). In the translocation group, 55% of eyes gained 3 lines or more at two years compared with 10% in the PDT group. Sixty percent of eyes in the translocation group vs 40% in the PDT group had an improvement of at least five letters. Mean foveal displacement after translocation was 906 mum; postoperative complications included retinal detachment (three eyes), macular fold (one eye), and transient diplopia (four eyes). In young patients, the postoperative gain was better in both groups. In the translocation group, mean survival time for choroidal neovascularization recurrence was 40 months for patients younger than 40 years and 20 months for older patients. CONCLUSIONS: Translocation showed better results than PDT at two years. Further studies are required to confirm these findings.


Assuntos
Neovascularização de Coroide/tratamento farmacológico , Neovascularização de Coroide/cirurgia , Macula Lutea/transplante , Miopia Degenerativa/complicações , Fotoquimioterapia , Acuidade Visual/fisiologia , Neovascularização de Coroide/etiologia , Feminino , Angiofluoresceinografia , Fóvea Central , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Resultado do Tratamento
10.
Dalton Trans ; (48): 5691-702, 2006 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-17146534

RESUMO

Three heterotetranuclear complexes, [{Ru(II)(bpy)(2)(L(n))}(3)Mn(II)](8+) (bpy = 2,2'-bipyridine, n = 2, 4, 6), in which a Mn(II)-tris-bipyridine-like centre is covalently linked to three Ru(II)-tris-bipyridine-like moieties using bridging bis-bipyridine L(n) ligands, have been synthesised and characterised. The electrochemical, photophysical and photochemical properties of these complexes have been investigated in CH(3)CN. The cyclic voltammograms of the three complexes exhibit two successive very close one-electron metal-centred oxidation processes in the positive potential region. The first, which is irreversible, corresponds to the Mn(II)/Mn(III) redox system (E(pa) approximately 0.82 V vs Ag/Ag(+) 0.01 M in CH(3)CN-0.1 M Bu(4)NClO(4)), whereas the second which is, reversible, is associated with the Ru(II)/Ru(III) redox couple (E(1/2) approximately 0.91 V). In the negative potential region, three successive reversible four electron systems are observed, corresponding to ligand-based reduction processes. The three stable dimeric oxidized forms of the complexes, [Mn(2)(III,IV)O(2){Ru(II)(bpy)(2)(L(n))}(4)](11+), [Mn(2)(IV,IV)O(2){Ru(II)(bpy)(2)(L(n))}(4)](12+) and [Mn(2)(IV,IV)O(2){Ru(III)(bpy)(2)(L(n))}(4)](16+) are obtained in fairly good yields by sequential electrolyses after consumption of respectively 1.5, 0.5 and 3 electrons per molecule of initial tetranuclear complexes. The formation of the di-micro-oxo binuclear complexes are the result of the instability of the {[Ru(II)(bpy)(2)(L(n))](3)Mn(III)}(9+) species, which react with residual water, via a disproportionation reaction and the release of one ligand, [Ru(II)(bpy)(2)(L(n))](2+). A quantitative yield can be obtained for these reactions if the electrochemical oxidations are performed in the presence of an added external base like 2,6-dimethylpyridine. Photophysical properties of these compounds have been investigated showing that the luminescence of the Ru(II)-tris-bipyridine-like moieties is little affected by the presence of manganese within the tetranuclear complexes. A slight quenching of the excited states of the ruthenium moieties, which occurs by an intramolecular process, has been observed. Measurements made at low concentration (<1 x 10(-5) M) indicate that some decoordination of Mn(2+) arises in 1a-c. These measurements allow the calculation of the association constants for these complexes. Finally, photoinduced oxidation of the tetranuclear complexes has been performed by continuous photolysis experiments in the presence of a large excess of a diazonium salt, acting as a sacrificial oxidant. The three successive oxidation processes, Mn(II)--> Mn(III)Mn(IV), Mn(III)Mn(IV)--> Mn(IV)Mn(IV) and Ru(II)--> Ru(III) are thus obtained, the addition of 2,6-dimethylpyridine in the medium giving an essentially quantitative yield for the two first photo-induced oxidation steps as found for electrochemical oxidation.


Assuntos
Compostos de Manganês/química , Compostos Organometálicos/química , Oxidantes Fotoquímicos/química , Compostos de Rutênio/química , Eletroquímica , Transporte de Elétrons , Compostos Organometálicos/síntese química , Oxidantes Fotoquímicos/síntese química , Oxirredução , Fotoquímica , Fótons
11.
Eur J Nucl Med Mol Imaging ; 32(6): 635-40, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15747155

RESUMO

PURPOSE: The purpose of this study was to determine the potential role of the sentinel lymph node (SLN) procedure in limited lymph node dissection in patients with apparently localised prostate carcinoma. METHODS: In 27 patients with organ-confined prostate cancer, a single injection of 0.3 ml/30 MBq( 99m)Tc-rhenium sulphur colloid was injected transrectally into the peripheral zone of each lobe of the prostate (total 0.6 ml/60 MBq) under ultrasound guidance. Two hours after injection, scintigraphy was performed. The first step in surgery was the detection and dissection of lymph nodes identified as SLNs. Then, standard lymphadenectomy was performed, consisting in a limited dissection that included all lymph nodes from the obturator fossa and along the external iliac vein. Lymphatic tissue along the hypogastric artery was not systematically removed, except in the presence of SLNs. RESULTS: Mean patient age was 66 years (48-77); the mean serum prostate-specific antigen value was 10.6 ng/ml. In a high proportion of patients (21/27, 77.8%) an SLN was located along the initial centimetres of the hypogastric artery. The second most frequent site of SLNs was in the obturator fossa (11/27 patients, 40.7%), followed by the external iliac area (5/27 patients, 18.5%). Four patients had lymph node metastases, all in SLNs: two in the hypogastric area and two in the obturator fossa. CONCLUSION: The SLN procedure revealed the individual variability in the lymphatic drainage of the prostate. The main site of SLNs was the hypogastric area, and two of the four metastatic nodes were located at this site. A limited standard pelvic lymphadenectomy, excluding the hypogastric lymph nodes, would have missed half of the lymph node metastases in this study. A radionuclide SLN procedure could assist in the correct staging of patients with early prostate cancer, especially when performing limited lymphadenectomy.


Assuntos
Excisão de Linfonodo/métodos , Linfonodos/diagnóstico por imagem , Linfonodos/cirurgia , Pelve/diagnóstico por imagem , Pelve/cirurgia , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/cirurgia , Cirurgia Assistida por Computador/métodos , Idoso , Humanos , Linfonodos/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Pelve/patologia , Neoplasias da Próstata/patologia , Cintilografia , Biópsia de Linfonodo Sentinela/métodos , Resultado do Tratamento
12.
Inorg Chem ; 43(20): 6313-23, 2004 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-15446878

RESUMO

The manganese(II) ion has many favorable properties that lead to its potential use as an MRI contrast agent: high spin number, long electronic relaxation time, labile water exchange. The present work describes the design, synthesis, and evaluation of a novel Mn(II) complex (MnL1) based on EDTA and also contains a moiety that noncovalently binds the complex to serum albumin, the same moiety used in the gadolinium based contrast agent MS-325. Ultrafiltration albumin binding measurements (0.1 mM, pH 7.4, 37 degrees C) indicated that the complex binds well to plasma proteins (rabbit: 96 +/- 2% bound, human: 93 +/- 2% bound), and most likely to serum albumin (rabbit: 89 +/- 2% bound, human 98 +/- 2% bound). Observed relaxivities (+/- 5%) of the complex were measured (20 MHz, 37 degrees C, 0.1 mM, pH 7.4) in HEPES buffer (r(1) = 5.8 mM(-)(1) s(-)(1)), rabbit plasma (r(1) = 51 mM(-)(1) s(-)(1)), human plasma (r(1) = 46 mM(-)(1) s(-)(1)), 4.5% rabbit serum albumin (r(1) = 47 mM(-)(1) s(-)(1)), and 4.5% human serum albumin (r(1) = 48 mM(-)(1) s(-)(1)). The water exchange rate was near optimal for an MRI contrast agent (k(298) = 2.3 +/- 0.9 x 10(8) s(-)(1)). Variable temperature NMRD profiles indicated that the high relaxivity was due to slow tumbling of the albumin-bound complex and fast exchange of the inner sphere water. The concept of a high relaxivity Mn(II)-based contrast agent was validated by imaging at 1.5 T. In a rabbit model of carotid artery injury, MnL1 clearly delineated both arteries and veins while also distinguishing between healthy tissue and regions of vessel damage.


Assuntos
Meios de Contraste , Manganês/química , Compostos Organometálicos , Animais , Meios de Contraste/síntese química , Meios de Contraste/química , Meios de Contraste/farmacocinética , Avaliação Pré-Clínica de Medicamentos , Humanos , Imagem por Ressonância Magnética , Manganês/sangue , Conformação Molecular , Compostos Organometálicos/síntese química , Compostos Organometálicos/química , Compostos Organometálicos/farmacocinética , Coelhos , Albumina Sérica/química , Temperatura
13.
J Org Chem ; 69(18): 5881-7, 2004 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-15373473

RESUMO

A calix[6]arene wheel, whose cavity has been extended and rigidified by N-phenylureido groups on the upper rim, forms pseudorotaxane species with molecular axles containing the viologen (4,4'-bipyridinium) unit in CH(2)Cl(2) solution. In these conditions, the self-assembly process is very efficient, with associated DeltaG degrees values of around -8 kcal mol(-1). The counteranions of the bipyridinium-based threads play indeed an important role in the formation of the complex. The use of either tosylate or hexafluorophosphate salts of the guests affects both the stability of the complexes and the rate of the threading process. Such effects have been interpreted in terms of ion-pair recognition, suggesting that coordination of the counteranions of the viologen thread by the ureido groups of the calixarene wheel is crucial for the breaking of tight ion pairs prior to threading. The rate constants of the threading/dethreading reactions coupled with the redox processes of the viologen unit of the axle have been obtained by means of cyclic voltammetry. The pseudorotaxane species undergo fast dethreading (submicrosecond time scale) on electrochemical reduction of the guest. The heterogeneous electron-transfer kinetics for the reduction of the viologen unit is slowed upon encapsulation into the calixarene cavity.

14.
Prog Urol ; 14(4): 501-6, 2004 Sep.
Artigo em Francês | MEDLINE | ID: mdl-15776899

RESUMO

OBJECTIVE: Use of an isotope sentinel node mapping technique in prostate cancer to study its feasibility, lymphatic prostate drainage and its value in pelvic lymph node staging. MATERIAL AND METHOD: The sentinel node mapping technique was performed in 34 patients with clinically localized prostate cancer. A transrectal intraprostatic injection of Technetium 99m-labelled nanocolloidal particles was performed on the day before radical prostatectomy. Sentinel node mapping was performed by intraoperative lymphoscintigraphy and gamma probe. A standard pelvic lymphadenectomy was systematically performed. RESULTS: Preoperative lymphoscintigraphy allowed identification of sentinel nodes in 85.3% of patients. Four of the five failures had a history of pelvic surgery. Sentinel node mapping and biopsy were possible in 23 patients (67.7%). The majority of sentinel nodes were located in the hypogastric region (58.4%). A microscopic lymph node metastasis was identified in 4 patients (11.7%), located in a sentinel node in 3 cases. In 2 cases, the micrometastasis was situated in a sentinel node outside of the pelvic chain. These four patients had a pretreatment PSA > 10 ng/ml and a Gleason score > or = 7 (on the prostatectomy specimen). CONCLUSION: This study confirms the feasibility of the sentinel node technique in prostate cancer and the diversity of lymphatic drainage of the prostate. Pelvic lymphadenectomy alone also appears to be insufficient for precise staging in patients with pretreatment PSA > 10 ng/ml and a Gleason score > 6. This isotope technique could therefore improve the yield of lymphadenectomy by limiting its extent.


Assuntos
Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Biópsia de Linfonodo Sentinela/métodos , Idoso , Desenho de Equipamento , Estudos de Viabilidade , Humanos , Masculino , Pessoa de Meia-Idade , Cintilografia , Contagem de Cintilação/instrumentação
15.
J Am Chem Soc ; 125(4): 987-94, 2003 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-12537497

RESUMO

The 4'-dimethylaminoflavylium ion in aqueous solution undergoes an intricate network of chemical reactions controlled by pH and light excitation. It is shown that nine different forms are involved, including two species that are not present in previously investigated compounds of the flavylium family. The thermodynamic and kinetic constants of the equilibria and interconversion processes have been obtained by pH jump (included stopped-flow) experiments. The photochromic properties exhibited by the trans/cis chalcone forms have been investigated. The peculiar aspect of 4'-dimethylaminoflavylium, as compared to previously investigated compounds of the same family, is a close to planarity structure, as demonstrated by the X-ray analysis on the parent 4'-aminoflavylium compound (2.3 degrees torsion angle between the benzopyrylium and benzene ring). The results obtained show that the flavylium cation is strongly stabilized by the electron-donor character of the dimethylamino substituent on the benzene ring. The donor-acceptor interaction makes both the protonation of the amino group and the hydration of the flavylium cation difficult, with consequences on the tautomerization and cis/trans isomerization reactions. The multistate/multifunctional properties of 4'-dimethylaminoflavylium have been discussed in the frame of write-lock-read-unlock-erase cycles.

16.
J Med Chem ; 45(16): 3465-74, 2002 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-12139457

RESUMO

Amphiphilic gadolinium complexes were investigated as potential magnetic resonance imaging (MRI) contrast agents. A series of complexes was synthesized in order to study the effect of hydrophilic phosphodiester groups on albumin binding, relaxivity, and blood half-life in rats. Thus, compound 11a, a diethylenetriaminepentaacetato aquo gadolinium(III) (Gd-DTPA) derivative with an octyl substituent, was synthesized and compared to 5b, the analogous octyl derivative containing a phosphodiester linkage between the gadolinium chelate and the alkyl chain. Likewise, 11b, a naphthyl Gd-DTPA derivative, was compared to the naphthyl phosphodiester derivative 5c. A direct comparison is not available for 5a, a 4,4-diphenylcyclohexyl phosphodiester Gd-DTPA derivative; however, its pharmacokinetic properties mirror those of the other phosphodiester derivatives. Although the introduction of the phosphodiester moiety decreased log P by approximately 1.7 units, albumin binding data obtained in 4.5% human serum albumin (HSA) indicated that derivatives containing the phosphodiester group exhibited somewhat higher albumin affinity than their alkyl analogues (54 +/- 5 and 44 +/- 4% for 5b and 11a, respectively; 40 +/- 4 and 30 +/- 3% for 5c and 11b, respectively). Both classes of agents were characterized by enhanced relaxivity in the presence of 4.5% HSA (r1 = 16-42 mM(-1) s(-1) at 20 MHz and 37 degrees C) as compared with the relaxivity values measured in phosphate-buffered saline (PBS) alone (r1 = 4.6-6.6 mM(-1) s(-1) at 20 MHz and 37 degrees C). Pharmacokinetic data indicated that compound 5b had a half-life of 14.3 +/- 1.8 min in the rat as compared with a half-life of 6.20 +/- 0.04 min for the non-phosphodiester analogue 11a. Similarly, the half-life obtained for the phosphodiester 5c was 14.3 +/- 1.7 min as compared with a half-life of 6.80 +/- 0.03 min for 11b. The percent biliary excretion was significantly lower for the phosphodiester compounds than for non-phosphodiester analogues (17.7 +/- 4.0 and 66.9 +/- 3.4% for 5b and 11a, respectively; 17.0 +/- 1.6 and 64.3 +/- 9.0% for 5c and 11b, respectively). The percent biliary excretion (15.8 +/- 4.4%) and plasma half-life in the rat (23.1 +/- 2.9 min) for 5a are consistent with the extended plasma half-life of the other phosphodiester derivatives. Taken together, the enhanced relaxivity and extended blood half-life of the phosphodiester derivatives support the concept of using endogenous albumin binding to achieve blood pool-like properties for small-molecule magnetic resonance imaging (MRI) contrast agents.


Assuntos
Meios de Contraste/química , Meios de Contraste/farmacocinética , Gadolínio DTPA/química , Gadolínio DTPA/farmacocinética , Gadolínio , Compostos Organometálicos/química , Compostos Organometálicos/farmacocinética , Organofosfatos/química , Albumina Sérica/metabolismo , Animais , Meios de Contraste/metabolismo , Meia-Vida , Imagem por Ressonância Magnética , Masculino , Compostos Organometálicos/sangue , Ligação Proteica , Ratos , Ratos Sprague-Dawley , Relação Estrutura-Atividade
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA