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1.
Pharmaceuticals (Basel) ; 17(7)2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-39065671

RESUMEN

Copper (Cu) is a critical element for cancer cell proliferation and considerably accumulates in the nucleus. 64Cu2+ is an anticancer radiopharmaceutical that targets the copper requirement of cancer cells. However, intravenously injected 64Cu2+ ions primarily accumulate in the liver. Ligand complexation of 64Cu2+ may be a promising method for increasing tumor delivery by reducing liver uptake. In this study, we used three tripodal amine ligands [tris(2-aminoethyl)amine (Tren), diethylenetriamine (Dien), and tris(2-pyridylmethyl)amine (TPMA)] to enclose 64Cu2+ ions and compared their in vivo tumor and liver uptakes using a tumor-bearing xenograft mouse model of the extrahepatic bile duct carcinoma cell line TFK-1. We examined intracellular Cu distribution using microparticle-induced X-ray emission (micro-PIXE) analysis of these compounds. 64Cu2+-Tren and 64Cu2+-Dien showed higher tumor uptake than 64Cu2+-TPMA and 64Cu2+ ions in TFK-1 tumors. Among the three 64Cu2+ complexes and 64Cu2+ ions, liver uptake was inversely correlated with tumor uptake. Micro-PIXE analysis showed that in vitro cellular uptake was similar to in vivo tumor uptake, and nuclear delivery was the highest for 64Cu2+-Tren. Conclusively, an inverse correlation between tumor and liver uptake was observed using three 64Cu2+ complexes of tripodal amine ligands and 64Cu2+ ions. These results provide useful information for the future development of anticancer 64Cu radiopharmaceuticals.

2.
Pharmaceuticals (Basel) ; 17(1)2023 Dec 21.
Artículo en Inglés | MEDLINE | ID: mdl-38275997

RESUMEN

[64Cu]Cu-diacetyl-bis(N4-methylthiosemicarbazone) ([64Cu]Cu-ATSM) is a radioactive hypoxia-targeting therapeutic agent being investigated in clinical trials for malignant brain tumors. For the quality management of [64Cu]Cu-ATSM, understanding trace metal impurities' effects on the chelate formation of 64Cu and ATSM is important. In this study, we conducted coordination chemistry studies on metal-ATSM complexes. First, the effects of nonradioactive metal ions (Cu2+, Ni2+, Zn2+, and Fe2+) on the formation of [64Cu]Cu-ATSM were evaluated. When the amount of Cu2+ or Ni2+ added was 1.2 mol or 288 mol, equivalent to ATSM, the labeling yield of [64Cu]Cu-ATSM fell below 90%. Little effect was observed even when excess amounts of Zn2+ or Fe2+ were added to the ATSM. Second, these metals were reacted with ATSM, and chelate formation was measured using ultraviolet-visible (UV-Vis) absorption spectra. UV-Vis spectra showed a rapid formation of Cu2+ and the ATSM complex upon mixing. The rate of chelate formation by Ni2+ and ATSM was lower than that by Cu-ATSM. Zn2+ and Fe2+ showed much slower reactions with the ATSM than Ni2+. Trace amounts of Ni2+, Zn2+, and Fe2+ showed little effect on [64Cu]Cu-ATSM' quality, while the concentration of impurity Cu2+ must be controlled. These results can provide process management tools for radiopharmaceuticals.

3.
Chemphyschem ; 21(17): 2019-2024, 2020 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-32767482

RESUMEN

Semiconductor nanomaterials with efficient polarized-light control in the blue region of the visible spectrum are promising candidates for modern and future photo-information technology, display devices, and optical sensing applications. New-type semiconductor Eu(OCN)2 nanocrystals with circularly polarized absorption (CD: circular dichroism) and emission (CPL: circularly polarized luminescence) under an applied magnetic field are demonstrated here for the first time. The effective CD signal at 1.6 T was observed at approximately 440 nm. The dissymmetry factor of CPL under 100 K, gM-CPL, was estimated to be 0.01. These characteristic circularly polarized absorption and emission phenomena of Eu(OCN)2 nanocrystals should be caused by combination between the "Faraday A and C terms" of the magnetic moment in the excited state. Polarized-light control using Eu(OCN)2 nanocrystals in the blue-light region of the electromagnetic spectrum is a large first step into a new world of photo-functional semiconductor nanomaterials.

4.
J Phys Condens Matter ; 29(36): 365802, 2017 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-28661405

RESUMEN

The synthesis, crystal structures and magnetic properties of Ba2La2MW2O12 (M = Mn, Co, Ni, Zn) were investigated. They crystallize in the 12-layer polytype of the perovskite structure with a regular cation defect in the B-site. The results of neutron diffraction measurements reveal that they adopt a rhombohedral structure with a space group R - 3 and have a cation ordering between Ba and La ions in the A-site. In these compounds, the magnetic M ions form the 2D triangular lattice. From the results of magnetic measurements, the ferromagnetic ordering of M2+ ions for M = Co (T C = 1.3 K) and Ni (6.2 K) and the paramagnetic behavior (T > 1.8 K) with an antiferromagnetic interaction for M = Mn are observed. From the DFT calculation, their band structures and magnetic interactions are discussed.

5.
Theranostics ; 7(7): 2048-2064, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28656060

RESUMEN

18F-Fluciclovine (trans-1-amino-3-18F-fluorocyclobutanecarboxylic acid; anti-18F-FACBC) is a positron emission tomography (PET) tracer for diagnosing cancers (e.g., prostate and breast cancer). The most frequent metastatic organ of these cancers is bone. Fluciclovine-PET can visualize bony lesions in clinical practice; however, such lesions have not been described histologically. Methods: We investigated the potential of 14C-fluciclovine in aiding the visualization of osteolytic and osteoblastic bone metastases (with histological analyses), compared with 3H-2-deoxy-2-fluoro-D-glucose (3H-FDG), 3H-choline chloride (3H-choline), and 99mTc-hydroxymethylene diphosphonate (99mTc-HMDP) by using triple-tracer autoradiography in rat breast cancer osteolytic (on day 12 ± 1 postinjection of MRMT-1) and prostate cancer osteoblastic (on day 20 ± 3 postinjection of AT6.1) metastatic models. Results: The distribution patterns of 14C-fluciclovine, 3H-FDG, and 3H-choline, but not 99mTc-HMDP, were similar in both models, and the lesions where these tracers accumulated were, histologically, typical osteolytic and osteoblastic lesions. 99mTc-HMDP accumulated mostly in osteoblastic lesions. 14C-fluciclovine could visualize the osteolytic lesions as early as day 6 postinjection of MRMT-1. However, differential distributions in 14C-fluciclovine and 3H-FDG existed, based on histological differences: low 14C-fluciclovine and high 3H-FDG accumulation in osteolytic lesions with inflammation. In the osteoblastic metastatic model, visualization of osteoblastic lesions with 14C-fluciclovine was not clear, yet clearer than with 3H-FDG. Although half of the osteoblastic lesions with 14C-fluciclovine accumulation showed negligible 3H-choline accumulation in comparison, they were histologically similar to lesions with marked 14C-fluciclovine and 3H-choline accumulation. Conclusion: These results suggest that fluciclovine-PET can visualize true osteolytic and osteoblastic bone metastatic lesions.


Asunto(s)
Neoplasias Óseas/diagnóstico por imagen , Neoplasias de la Mama/secundario , Ácidos Carboxílicos/administración & dosificación , Ciclobutanos/administración & dosificación , Metástasis de la Neoplasia/diagnóstico por imagen , Tomografía de Emisión de Positrones/métodos , Neoplasias de la Próstata/secundario , Radiofármacos/administración & dosificación , Animales , Modelos Animales de Enfermedad , Masculino , Ratas
6.
Int J Mol Sci ; 18(5)2017 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-28468238

RESUMEN

18F-fluciclovine (trans-1-amino-3-18F-fluorocyclobutanecarboxylic acid) is an amino acid positron emission tomography (PET) tracer used for cancer staging (e.g., prostate and breast). Patients scheduled to undergo amino acid-PET are usually required to fast before PET tracer administration. However, there have been no reports addressing whether fasting improves fluciclovine-PET imaging. In this study, the authors investigated the influence of fasting on fluciclovine-PET using triple-tracer autoradiography with 14C-fluciclovine, [5,6-³H]-2-fluoro-2-deoxy-d-glucose (³H-FDG), and 99mTc-hydroxymethylene diphosphonate (99mTc-HMDP) in a rat breast cancer model of mixed osteolytic/osteoblastic bone metastases in which the animals fasted overnight. Lesion accumulation of each tracer was evaluated using the target-to-background (muscle) ratio. The mean ratios of 14C-fluciclovine in osteolytic lesions were 4.6 ± 0.8 and 2.8 ± 0.6, respectively, with and without fasting, while those for ³H-FDG were 6.9 ± 2.5 and 5.1 ± 2.0, respectively. In the peri-tumor bone formation regions (osteoblastic), where 99mTc-HMDP accumulated, the ratios of 14C-fluciclovine were 4.3 ± 1.4 and 2.4 ± 0.7, respectively, and those of ³H-FDG were 6.2 ± 3.8 and 3.3 ± 2.2, respectively, with and without fasting. These results suggest that fasting before 18F-fluciclovine-PET improves the contrast between osteolytic and osteoblastic bone metastatic lesions and background, as well as 18F-FDG-PET.


Asunto(s)
Neoplasias Óseas/diagnóstico por imagen , Neoplasias Óseas/secundario , Huesos/diagnóstico por imagen , Ácidos Carboxílicos/análisis , Medios de Contraste/análisis , Ciclobutanos/análisis , Tomografía de Emisión de Positrones/métodos , Animales , Neoplasias de la Mama/diagnóstico por imagen , Línea Celular Tumoral , Ayuno , Femenino , Fluorodesoxiglucosa F18/análisis , Masculino , Ratas , Ratas Sprague-Dawley , Medronato de Tecnecio Tc 99m/análogos & derivados , Medronato de Tecnecio Tc 99m/análisis
7.
Inorg Chem ; 56(5): 2459-2466, 2017 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-28199088

RESUMEN

The synthesis, crystal structures, photoluminescence, and magnetic properties of the melilite-type oxysulfide Sr2MnGe2S6O were investigated. This compound crystallizes in the melilite structure with space group P4̅21m, in which two kinds of anions, S2- and O2-, occupy different crystallographic sites in an ordered manner. The temperature dependence of the magnetic susceptibility of Sr2MnGe2S6O shows a broad peak due to a two-dimensional magnetic interaction between Mn ions in the ab plane. The specific heat data show that this compound has an antiferromagnetic transition temperature (TN = 15.5 K) that is much higher than that of the oxide analogue Sr2MnGe2O7 (TN = 4.4 K). DFT calculations showed that the magnetic interaction is enhanced by covalency in the Mn-S bonding.

8.
J Clin Endocrinol Metab ; 101(3): 1008-15, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26756116

RESUMEN

CONTEXT: Although adrenal vein sampling is the standard method to distinguish unilateral from bilateral forms of primary aldosteronism, it is an invasive and technically difficult procedure. (11)C-metomidate (MTO)-positron emission tomography was reported as a potential replacement for adrenal vein sampling. However, MTO has low selectivity for CYP11B2 over CYP11B1. OBJECTIVE: This study aimed to determine the selectivity of (18)F-CDP2230, a new imaging agent, for CYP11B2 over CYP11B1 and determine whether the biodistribution profile of (18)F-CDP2230 is favorable for imaging CYP11B2. METHODS: The IC50 of CDP2230 for the enzymatic activities of CYP11B2 and CYP11B1 was determined using cells with stable expression of either enzyme. In vitro autoradiography of human adrenal sections with aldosterone-producing adenomas was performed to confirm the specific binding ability of (18)F-CDP2230 to CYP11B2-expressing regions. Furthermore, positron emission tomography and magnetic resonance imaging were performed to evaluate the biodistribution of (18)F-CDP2230 in rats. RESULTS: Although CDP2230 showed a significantly lower affinity for CYP11B2 and CYP11B1 than did MTO analogues, its selectivity for CYP11B2 over CYP11B1 was higher than that of MTO analogues. In vitro autoradiography revealed that the binding of (18)F-CDP2230 to CYP11B2-expressing regions in the adrenal gland was more specific than that of (123)I-IMTO. Moreover, the biodistribution study showed that (18)F-CDP2230 accumulated in adrenal glands with low background uptake. CONCLUSIONS: Our study showed a high selectivity of (18)F-CDP2230 for CYP11B2 over CYP11B1 with a favorable biodistribution for imaging CYP11B2. (18)F-CDP2230 is a promising imaging agent for detecting unilateral subtypes of primary aldosteronism.


Asunto(s)
Bencimidazoles , Citocromo P-450 CYP11B2/análisis , Hiperaldosteronismo/clasificación , Hiperaldosteronismo/enzimología , Adenoma/enzimología , Neoplasias de las Glándulas Suprarrenales/enzimología , Glándulas Suprarrenales/enzimología , Aldosterona/biosíntesis , Aldosterona/metabolismo , Animales , Autorradiografía , Línea Celular , Cricetinae , Cricetulus , Femenino , Radioisótopos de Flúor , Humanos , Inmunohistoquímica , Imagen por Resonancia Magnética , Masculino , Tomografía de Emisión de Positrones , Trazadores Radiactivos , Ratas , Ratas Wistar , Sensibilidad y Especificidad , Esteroide 11-beta-Hidroxilasa/análisis
9.
Inorg Chem ; 54(22): 10725-31, 2015 Nov 16.
Artículo en Inglés | MEDLINE | ID: mdl-26496353

RESUMEN

The synthesis, crystal structures, and magnetic properties of the pentanary oxides PbM2Ni6Te3O18 (M = Mn and Cd) were investigated. These compounds crystallize in a hexagonal structure with space group P63/m, in which the Ni(2+) ions form a zigzag chain along the c axis. From the magnetic susceptibility and specific heat measurements, we found that the PbCd2Ni6Te3O18 behaves as a low-dimensional magnet due to the intrachain antiferromagnetic interaction between Ni(2+) ions. Both compounds show a long-range antiferromagnetic ordering at 25.7 K (M = Cd) and 86.0 K (Mn). The magnetic structure of PbMn2Ni6Te3O18 determined by neutron diffraction measurements is a collinear antiferromagnetic arrangement of Mn(2+) ions in the Mn2O9 dimeric unit and Ni(2+) ions in the zigzag chain.

10.
Nucl Med Biol ; 42(8): 664-72, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-26022202

RESUMEN

INTRODUCTION: Magnetic resonance imaging (MRI) can have a problem to delineate diffuse gliomas with an intact blood-brain barrier (BBB) especially when a marked peritumoral edema is present. We evaluated the potential of trans-1-amino-3-(18)F-fluorocyclobutanecarboxylic acid (anti-(18)F-FACBC) positron emission tomography (PET) to delineate the extent of diffuse gliomas by comparing PET findings with autoradiography, in vivo and ex vivo MRI, and histopathology findings. METHODS: Dynamic PET was performed in rats with N-ethyl-N-nitrosourea-induced glioma for 60 min after anti-(18)F-FACBC injection. Contrast-enhanced MRI was performed before or after PET. The PET images were fused with in vivo and ex vivo MR images, and histopathological images for direct comparisons. Autoradiograms were compared with the results of Evans Blue (EB) extravasation (to assess BBB integrity) and hematoxylin-eosin staining. RESULTS: Histopathological examination, including EB extravasation assessment, and enhanced T1-weighted MRI identified several diffuse gliomas with slight BBB disruption, similar to low-grade human gliomas. Anti-(18)F-FACBC uptake was specific and high in the gliomas, irrespective of BBB integrity. Higher anti-(18)F-FACBC uptake corresponded to areas of T2 hyperintensity, independent of gadolinium enhancement. Ex vivo autoradiography also showed high anti-(18)F-FACBC accumulation in tumors lacking EB extravasation and a correlation between anti-(18)F-FACBC accumulation and tumor cell density, but not EB extravasation. CONCLUSIONS: Anti-(18)F-FACBC-PET allowed visualization of gliomas irrespective of BBB integrity. The tumor-to-normal uptake ratio of anti-(18)F-FACBC generally correlated with the relative cell density. Anti-(18)F-FACBC PET combined with MRI shows promise for preoperative glioma delineation. ADVANCES IN KNOWLEDGE: Radiopharmaceuticals that cross the BBB, such as anti-(18)F-FACBC, are taken up by low-grade gliomas with equivocal MRI findings due to an intact BBB. IMPLICATIONS FOR PATIENT CARE: Surgery is the first-line therapy for low-grade gliomas; therefore, delineation of their extent in the presence of an intact BBB is essential to planning surgery that removes the entire neoplasm, which will positively affect long-term survival.


Asunto(s)
Ácidos Carboxílicos/farmacocinética , Ciclobutanos/farmacocinética , Glioma/diagnóstico por imagen , Glioma/patología , Tomografía de Emisión de Positrones/métodos , Radiofármacos/farmacocinética , Alquilantes/toxicidad , Animales , Autorradiografía , Barrera Hematoencefálica/diagnóstico por imagen , Barrera Hematoencefálica/efectos de los fármacos , Barrera Hematoencefálica/patología , Neoplasias Encefálicas/inducido químicamente , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/patología , Etilnitrosourea/toxicidad , Femenino , Radioisótopos de Flúor/farmacocinética , Glioma/inducido químicamente , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Clasificación del Tumor , Ratas , Ratas Endogámicas F344 , Distribución Tisular
11.
Nucl Med Biol ; 42(7): 598-607, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25892210

RESUMEN

INTRODUCTION: We examined whether the amino acid PET tracers, trans-1-amino-3-(18)F-fluorocyclobutanecarboxylic acid (anti-(18)F-FACBC) and (11)C-methyl-l-methionine ((11)C-Met), are suitable for detecting early responses to combination therapies including temozolomide (TMZ), interferon-ß (IFN), and bevacizumab (Bev) in glioblastoma. METHODS: Human glioblastoma U87MG (U87) cells were incubated with low dose TMZ to induce chemoresistance. Both trans-1-amino-3-fluoro-1-(14)C-cyclobutanecarboxylic acid (anti-(14)C-FACBC) and (3)H-methyl-l-methionine ((3)H-Met) uptake were quantified using triple-label accumulation assays to examine the relationship between tracer uptake and proliferation ((3)H-thymidine (TdR) accumulation) in vitro. U87 and U87R (TMZ-resistant subculture) cells were inoculated into the right and left basal ganglia, respectively, of F344/N-rnu rats. The efficacy of single-agent (TMZ, Bev) and combination therapy (TMZ/IFN, TMZ/Bev, TMZ/IFN/Bev) was examined in orthotopic gliomas using MRI, Evans blue extravasation, anti-(14)C-FACBC, and (3)H-Met autoradiography, and MIB-1 immunostaining. RESULTS: TMZ treatment decreased (3)H-TdR accumulation and the volume distribution of anti-(14)C-FACBC and (3)H-Met in U87 but not U87R cells. TMZ/IFN combination therapy significantly decreased these parameters in U87R cells; however, Bev had no additional effect in vitro. In vivo, U87R-derived gliomas were observed as equivocal tumors on MRI and T2-high intensity lesions. Bev treatment, either alone or in combination, markedly decreased U87 enhancing lesions. By contrast, autoradiographic images using anti-(14)C-FACBC and (3)H-Met clearly delineated tumor extent, which spread widely beyond T2-high intensity lesions and enhancing lesions. TMZ therapy significantly decreased tracer accumulation and proliferation of U87- but not U87R-derived tumors. TMZ/IFN combination treatment significantly decreased these parameters in U87R tumors, which were further reduced (in both tumor types) by Bev addition. Tracer uptake correlated with the MIB-1 proliferation index. However, MRI was unsuitable for tumor delineation and assessment of Bev treatment response. CONCLUSIONS: Triple-agent therapy (TMZ/IFN/Bev) was effective against even TMZ-resistant glioblastomas. PET with amino acid tracers provides useful information on the early response of glioblastomas to single-agent and combination therapy.


Asunto(s)
Aminoácidos/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/metabolismo , Glioblastoma/tratamiento farmacológico , Glioblastoma/metabolismo , Animales , Antineoplásicos/administración & dosificación , Bevacizumab/administración & dosificación , Biomarcadores de Tumor/metabolismo , Neoplasias Encefálicas/diagnóstico por imagen , Línea Celular Tumoral , Dacarbazina/administración & dosificación , Dacarbazina/análogos & derivados , Glioblastoma/diagnóstico por imagen , Humanos , Interferón beta/administración & dosificación , Masculino , Tomografía de Emisión de Positrones/métodos , Radiofármacos/farmacocinética , Ratas , Ratas Endogámicas F344 , Ratas Desnudas , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Temozolomida , Distribución Tisular , Resultado del Tratamiento
12.
Inorg Chem ; 53(14): 7635-41, 2014 Jul 21.
Artículo en Inglés | MEDLINE | ID: mdl-24956446

RESUMEN

The effective magneto-optical properties of novel nonanuclear Tb(III) complexes with Tb-O lattice (specifically, [Tb9(sal-R)16(µ-OH)10](+)NO3(-), where sal-R = alkyl salicylate (R = -CH3 (Me), -C2H5 (Et), -C3H7 (Pr), or -C4H9 (Bu)) are reported. The geometrical structures of these nonanuclear Tb(III) complexes were characterized using X-ray single-crystal analysis and shape-measure calculation. Optical Faraday rotation was observed in nonanuclear Tb(III) complexes in the visible region. The Verdet constant per Tb(III) ion of the Tb9(sal-Me) complex is 150 times larger than that of general Tb(III) oxide glass. To understand their large Faraday rotation, electron paramagnetic resonance measurements of Gd(III) complexes were carried out. In this Report, the magneto-optical relation to the coordination geometry of Tb ions is discussed.

13.
Nucl Med Biol ; 41(7): 545-51, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24816330

RESUMEN

INTRODUCTION: Trans-1-amino-3-[(18)F]fluorocyclobutanecarboxylic acid (anti-[(18)F]FACBC) is a positron emission tomography (PET) tracer used to visualize prostate cancer (PCa). In this study, we investigated the differences in anti-[(18)F]FACBC accumulation between metastatic and inflamed lymph node (LN) lesions. METHODS: A PCa LN metastasis (PLM) model was developed by inoculating a rat PCa cell line, MAT-Ly-Lu-B2, into popliteal LNs of Copenhagen rats. Acute lymphadenitis (AL) was induced by injecting concanavalin A (Con A) into the hind footpad, and chronic lymphadenitis (CL) was induced by daily injection of Con A into the tissues surrounding the popliteal LNs for 2weeks. Main lesions of all animal models were established in lumbar and/or inguinal LNs. Biodistribution and dynamic PET imaging data were acquired after tracer injection. T2-weighted magnetic resonance (MR) images were registered with PET images. RESULTS: In the biodistribution study, the uptake ratios of PLM-to-lymphadenitis in lesional lumbar and inguinal LNs were 0.97-1.57 and 1.47-2.08 at 15 and 60min post-anti-[(18)F]FACBC injection respectively. In PET imaging, the lesional lumbar LNs of CL and PLM, but not of AL, were visualized on anti-[(18)F]FACBC-PET/MR fusion images without disturbance from radioactivity from urine, and the rank order of anti-[(18)F]FACBC accumulation at 50-60 post-injection in lesional lumbar LNs was PLM>CL>AL. CONCLUSIONS: Anti-[(18)F]FACBC accumulation in LNs with PLM was higher than that in inflamed LNs. ADVANCES IN KNOWLEDGE: The study showed that although low but significant levels of anti-[(18)F]FACBC uptake by chronic inflamed lesions might cause false-positives in anti-[(18)F]FACBC-PET in some PCa patients, uptake of the tracer at acutely inflamed sites was minimal. IMPLICATIONS FOR PATIENT CARE: The findings of this study suggest the potential of Anti-[(18)F]FACBC for distinguishing between tumors and acute inflammation in clinical practice.


Asunto(s)
Ácidos Carboxílicos/metabolismo , Ciclobutanos/metabolismo , Linfadenitis/metabolismo , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Animales , Ácidos Carboxílicos/farmacocinética , Línea Celular Tumoral , Ciclobutanos/farmacocinética , Linfadenitis/diagnóstico por imagen , Metástasis Linfática , Masculino , Tomografía de Emisión de Positrones , Neoplasias de la Próstata/diagnóstico por imagen , Ratas , Distribución Tisular
14.
Nucl Med Biol ; 40(6): 808-15, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23701701

RESUMEN

INTRODUCTION: Amino acid PET tracers are promising for visualizing gliomas and evaluating radiochemotherapeutic effects. We compared the glioma detection and early response assessment utility between trans-1-amino-3-fluoro-1-(14)C-cyclobutanecarboxylic acid (anti-(14)C-FACBC) and (3)H-methyl-l-methionine ((3)H-Met) by simultaneously analyzing their uptake by rat gliomas treated with and without temozolomide (TMZ) in vitro and in vivo. METHODS: C6 rat gliomas were incubated with low-dose TMZ to induce chemoresistance. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay demonstrated a significantly greater surviving fraction in the TMZ-resistant subline (C6R) than in drug-naive cells (C6). The anti-(14)C-FACBC and (3)H-Met uptakes were quantified using a triple-label accumulation assay to examine the relationship between tracer uptake and proliferation ((3)H-thymidine (TdR) accumulation rate) in tumor cells. C6 and C6R cells were inoculated into the right and left basal ganglia, respectively, of rats. Efficacy of TMZ against the orthotopic gliomas was analyzed by MRI, Evans blue extravasation, anti-(14)C-FACBC and (3)H-Met autoradiography, and MIB-5 proliferation index. RESULTS: The (3)H-TdR accumulation rate and amino acid tracer (anti-(14)C-FACBC and (3)H-Met) uptake significantly decreased 48 and 72 h, respectively, after TMZ treatment in C6 but not C6R cells. Anti-(14)C-FACBC uptake correlated significantly with (3)H-Met uptake and the (3)H-TdR accumulation rate. In the intracerebral glioma model, anti-(14)C-FACBC and (3)H-Met autoradiography clearly delineated the tumor extent, which spread well beyond the high-T2-intensity and enhancing lesions visible on MRI and Evans blue extravasation. TMZ significantly decreased anti-(14)C-FACBC and (3)H-Met uptake and the MIB-5 index of C6 but not C6R tumors. TMZ inhibited tracer uptake and tumor proliferation before morphological changes on MRI. CONCLUSIONS: Anti-(14)C-FACBC, like (3)H-Met, was more sensitive than post-contrast T1-weighted MRI for detecting tumor extent and early tumor response to TMZ treatment. Anti-(18)F-FACBC should be a sensitive and precise imaging biomarker for tumor extent visualization and response assessment in glioma patients.


Asunto(s)
Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/tratamiento farmacológico , Ácidos Carboxílicos , Ciclobutanos , Glioma/diagnóstico , Glioma/tratamiento farmacológico , Imagen por Resonancia Magnética/métodos , Metionina/análogos & derivados , Animales , Barrera Hematoencefálica/metabolismo , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Ácidos Carboxílicos/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Ciclobutanos/metabolismo , Dacarbazina/análogos & derivados , Dacarbazina/farmacología , Dacarbazina/uso terapéutico , Estudios de Factibilidad , Glioma/metabolismo , Glioma/patología , Masculino , Metionina/metabolismo , Permeabilidad , Ratas , Temozolomida , Resultado del Tratamiento
15.
J Am Chem Soc ; 135(7): 2659-66, 2013 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-23343325

RESUMEN

Novel EuS nanocrystals containing paramagnetic Mn(II), Co(II), or Fe(II) ions have been reported as advanced semiconductor materials with effective optical rotation under a magnetic field, Faraday rotation. EuS nanocrystals with transition-metal ions, EuS:M nanocrystals, were prepared by the reduction of the Eu(III) dithiocarbamate complex tetraphenylphosphonium tetrakis(diethyldithiocarbamate)europium(III) with transition-metal complexes at 300 °C. The EuS:M nanocrystals thus prepared were characterized using X-ray diffraction (XRD), transmission electron microscopy (TEM), inductively coupled plasma atomic emission spectroanalysis (ICP-AES), and a superconducting quantum interference device (SQUID) magnetometer. Enhanced Faraday rotations of the EuS:M nanocrystals were observed around 550 nm, and their enhanced spin polarization was estimated using electron paramagnetic resonance (EPR) measurements. In this report, the magneto-optical relationship between the Faraday rotation efficiency and spin polarization is discussed.

16.
Inorg Chem ; 51(6): 3572-8, 2012 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-22375704

RESUMEN

The crystal structures and magnetic properties of melilite-type oxides Sr(2)MGe(2)O(7) (M = Mn, Co) were investigated. These compounds crystallize in the melilite structure with space group P ̅42(1)m, in which the M and Ge ions occupy two kinds of tetrahedral sites in an ordered manner. The magnetic M ions form a square-planar lattice in the ab plane. Both compounds do not show the structural phase transition down to 2.5 K. The temperature dependence of magnetic susceptibility for Sr(2)MnGe(2)O(7) shows a broad peak at ~6.0 K because of a two-dimensional magnetic interaction between Mn ions in the ab plane. At 4.4 K, an antiferromagnetic transition was observed. The magnetic structure was determined by the neutron powder diffraction measurements at 2.5 K. It can be represented by the propagation vector k = (0, 0, 1/2), and the magnetic moments of Mn(2+) (3.99 µ(B)) ions order antiferromagnetically in a collinear manner along the c axis. On the other hand, Sr(2)CoGe(2)O(7) shows an antiferromagnetic transition at 6.5 K with divergence between zero-field-cooled and field-cooled susceptibilities. Its magnetic structure determined at 2.5 K has a magnetic propagation vector k = (0, 0, 0), and the ordered magnetic moment of Co(2+) (2.81 µ(B)) adopts a collinear arrangement lying on the ab plane.

17.
Inorg Chem ; 49(23): 10809-14, 2010 Dec 06.
Artículo en Inglés | MEDLINE | ID: mdl-21033688

RESUMEN

Synthesis, crystal structures, and magnetic properties of melilite-type oxides A(2)MSi(2)O(7) (A = Sr, Eu; M = Mg, Mn) were investigated. These compounds crystallize in the melilite structure with space group P4̅2(1)m. The (151)Eu Mössbauer measurements show that the Eu ions are in the divalent state. The Eu(2)MgSi(2)O(7) is paramagnetic down to 1.8 K. Long-range antiferromagnetic ordering is observed at 3.4 K for Sr(2)MnSi(2)O(7). On the other hand, the Eu(2)MnSi(2)O(7) shows a ferrimagnetic transition at 10.7 K. From the magnetization and specific heat measurements, it is found that the Eu(2+) (14 µ(B)) and Mn(2+) (5 µ(B)) sublattices order antiferromagnetically. This result indicates that an interaction between f-d electrons (Eu-Mn) predominantly operate in this compound.

18.
Magn Reson Med ; 62(5): 1129-39, 2009 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-19780181

RESUMEN

A unique acquisition method is proposed for quantitative, high-sensitivity (19)F MR spectroscopic imaging for the study of drug distribution aiming at nmol-level metabolite information in mice. The use of fast spin echo (FSE) at 9.4T allowed us to obtain whole-body images with minimal effect of magnetic susceptibility and to acquire several metabolite signals simultaneously by the method of interleaved multifrequency selection. Modified 2-shot FSE was designed for simultaneous, high-sensitivity (19)F imaging and T(2) mapping. A time course study including all the main metabolites at 10-minute resolution was attained with an oral dose of 1-2 mmol 5-fluorouracil (5-FU) (130-260 mg)/kg in mice. With acquisition parameters optimized for in vivo T(2) of 40 ms, images of F-nucleotides/-sides, effective anabolites of the anticancer drug 5-FU, were obtained at the level of 200 nmol in the tumor for all the mice studied with a linear correlation (R = 0.96) between image intensity and the quantity determined in the excised tissue. The method exhibits potential capability of molecular imaging with a variety of (19)F-labeled compounds and drug evaluation.


Asunto(s)
Carcinoma Hepatocelular/metabolismo , Radioisótopos de Flúor/farmacocinética , Fluorouracilo/farmacocinética , Espectroscopía de Resonancia Magnética/métodos , Nucleótidos/metabolismo , Imagen de Cuerpo Entero/métodos , Administración Oral , Animales , Antineoplásicos , Carcinoma Hepatocelular/diagnóstico por imagen , Línea Celular Tumoral , Femenino , Fluorouracilo/administración & dosificación , Ratones , Ratones Endogámicos C3H , Especificidad de Órganos , Cintigrafía , Radiofármacos/farmacocinética , Distribución Tisular
19.
Inorg Chem ; 48(20): 9952-7, 2009 Oct 19.
Artículo en Inglés | MEDLINE | ID: mdl-19769336

RESUMEN

The crystal structures and characterizations of Ba(4)EuM(3)O(12) (M = Ru and Ir) are reported. They crystallize in a monoclinic 12-l-perovskite-type structure with space group C2/m. The M(3)O(12) trimers and EuO(6) octahedra are alternately linked by corner-sharing and form the perovskite-type structure with 12 layers. The (151)Eu Mossbauer and X-ray photoelectron spectra reveal that the Eu and M ions are in the trivalent and mixed valence (+4.33) oxidation states, respectively. Their electrical conductivities show semiconducting behavior with an activation energy of approximately 0.2 eV above room temperature and demonstrate two-dimensional Mott variable range hopping behavior at low temperatures. The magnetic susceptibility and specific heat measurements indicate that an antiferromagnetic ordering occurs at 4 K, which is due to the magnetic interaction between Ru(3)O(12) trimers. On the other hand, the Ir(3)O(12) trimer is found to be nonmagnetic.

20.
J Phys Condens Matter ; 21(4): 046006, 2009 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-21715833

RESUMEN

Crystal structures and magnetic properties of quaternary oxides MTeMoO(6) (M = Mn and Zn) were investigated. From the Rietveld analyses for the powder x-ray and neutron diffraction measurements, their detailed structures have been determined. Both compounds have orthorhombic structure with space group P 2(1)2(1)2 and a charge configuration of M(2+)Te(4+)Mo(6+)O(6). ZnTeMoO(6) shows diamagnetic behavior. In this structure, M ions are arranged in a square-planar manner. The temperature dependence of the magnetic susceptibility for MnTeMoO(6) shows a broad peak at ∼33 K, which is due to a two-dimensional characteristic of the magnetic interaction. In addition, this compound shows an antiferromagnetic transition at 20 K. The magnetic structure was determined by the powder neutron diffraction measurement at 3.3 K. The magnetic moments of Mn(2+) ions (4.45 µ(B)) order in a collinear antiferromagnetic arrangement along the b axis.

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