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1.
G Ital Nefrol ; 37(2)2020 Apr 09.
Artigo em Italiano | MEDLINE | ID: mdl-32281763

RESUMO

In recent years imaging techniques that use radionuclides have become more and more clinically relevant as they can provide functional information for specific anatomical districts. This has also involved nephrology, where radionuclides are used to study patients with different degrees of renal function failure up to terminal uremia. Although chronic kidney disease, and dialysis in particular, may affect the distribution and the elimination of radiopharmaceuticals, to date there are no consistent data on the risks associated with their use in this clinical context. In addition to the lack of data on the safety of radio-exposure in dialysis patients, there is also a shortage of information concerning the risk for healthcare staff involved in conducting the dialysis sessions performed after a nuclear test. This study, performed on 29 uremic patients who underwent hemodialysis immediately after a scintigraphic examination, assessed the extent of radio-contamination of the staff and of hemodialysis devices such as monitor, kits and dialysate. The data collected has been used to quantify the radiological risk in dialysis after the exposure to the most common radionuclides.


Assuntos
Falência Renal Crônica/diagnóstico por imagem , Compostos Radiofarmacêuticos/metabolismo , Diálise Renal , Soluções para Diálise/química , Soluções para Diálise/metabolismo , Humanos , Falência Renal Crônica/metabolismo , Cintilografia/efeitos adversos , Cintilografia/métodos , Compostos Radiofarmacêuticos/efeitos adversos , Medição de Risco , Uremia/metabolismo
2.
PLoS One ; 15(2): e0228848, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32050000

RESUMO

We investigated the relation of 99mTc-MIBI uptake to mitochondrial membrane potential (MMP) in cancer cell lines and patient-derived tumor cells (PDCs). In T47D and HT29 cells with low MDR1 expression, FCCP dose-dependently reduced MMP and 99mTc-MIBI accumulation in similar patterns with nearly perfect linear relationships. T47D and HT29 cells with high MDR1 expression had low 99mTc-MIBI accumulation that was minimally affected by FCCP dose. In these cells, verapamil markedly increased 99mTc-MIBI accumulation to magnitudes that were excessive compared to MMP increase. Decreased plasma membrane potential by verapamil and its recovery by FCCP suggested that enhanced 99mTc-MIBI transport through modified plasma membranes contributed to the excess accumulation. Evaluation of three different colon cancer PDCs with low to modest MDR1 expression verified that FCCP significantly suppressed MMP and similarly reduced 99mTc-MIBI accumulation. Verapamil partially recovered both MMP and 99mTc-MIBI accumulation that was lowered by FCCP. Importantly, a high linear correlation was found (r = 0.865) between 99mTc-MIBI accumulation and MMP in these cells. These findings indicate that low baseline 99mTc-MIBI uptake that is markedly increased by verapamil represents cancer cells with high levels of MDR1 expression. However, in cancer cells with low or modest levels of MDR1 expression that do not markedly increase 99mTc-MIBI uptake by verapamil, the magnitude of uptake is largely dependent on cellular MMP.


Assuntos
Transporte Biológico/fisiologia , Potencial da Membrana Mitocondrial/fisiologia , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Tecnécio Tc 99m Sestamibi/metabolismo , Verapamil/farmacologia , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Membrana Celular/metabolismo , Resistência a Múltiplos Medicamentos/fisiologia , Células HT29 , Humanos , Compostos Radiofarmacêuticos/metabolismo , Células Tumorais Cultivadas
3.
PLoS One ; 15(1): e0226495, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31929534

RESUMO

INTRODUCTION: Autoimmune reactions in Graves' disease (GD) occur not only in the thyroid gland, but also in the orbital connective tissue, eyelids, extraocular muscles. The occurrence of orbitopathy in the course of GD is influenced by environmental factors, e.g. cigarette smoking. OBJECTIVES: The aim of the study was to analyze the effect of cigarette smoking on the efficacy of activity of radioiodine(131I) therapy in patients with GD. We also studied the influence of cigarette smoking and the efficacy of prednisone prophylaxis on the risk of thyroid-associated ophthalmopathy (TAO) development after radioiodine therapy (RIT) during two years of follow-up. PATIENTS AND METHODS: Medical records of hyperthyroid patients treated with radioiodine had been included. Patients were scheduled to visit outpatient clinics at baseline and 1, 3, 6, 9, 12, 18, and 24 months after RIT. RESULTS: The studied group consisted of 336 patients (274 women, 62 men) diagnosed with GD and treated with RIT; 130 patients received second therapeutic dose of 131I due to recurrent hyperthyroidism. Among all studied patients, 220 (65.5%) were smokers and 116 (34.5%) non-smokers. In the group of smokers 115 (52.2%) of patients received single RIT, 105 (47.8%) received second dose of RAI due to recurrent hyperthyroidism. In non-smokers 91 (78.6%) received single activity of RAI, while 25 (21.4%) patients required second RIT due to recurrent hyperthyroidism. The ophthalmic symptoms in the group of smokers after RIT were less frequent, if the patient received preventative treatment in the form of oral prednisone (P = 0.0088). CONCLUSIONS: The results of our study suggest that cigarette smoking reduces the efficacy of treatment with 131I in patients with GD. The study also confirmed the effectiveness of steroid prophylaxis against TAO development or exacerbation after RIT.


Assuntos
Doença de Graves/radioterapia , Compostos Radiofarmacêuticos/uso terapêutico , Adulto , Idoso , Anti-Inflamatórios/uso terapêutico , Fumar Cigarros , Feminino , Doença de Graves/tratamento farmacológico , Oftalmopatia de Graves/diagnóstico , Oftalmopatia de Graves/tratamento farmacológico , Humanos , Hipertireoidismo/diagnóstico , Hipertireoidismo/patologia , Radioisótopos do Iodo/química , Radioisótopos do Iodo/metabolismo , Masculino , Pessoa de Meia-Idade , Prednisona/uso terapêutico , Compostos Radiofarmacêuticos/química , Compostos Radiofarmacêuticos/metabolismo , Recidiva , Estudos Retrospectivos , Tireotropina/sangue , Tiroxina/sangue , Tri-Iodotironina/sangue , Adulto Jovem
4.
Chemistry ; 26(6): 1238-1242, 2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-31743504

RESUMO

We report the first targeted nuclear medicine application of the lanthanum radionuclides 132/135 La. These isotopes represent a matched pair for diagnosis via the positron emissions of 132 La and therapy mediated by the Auger electron emissions of 135 La. We identify two effective chelators, known as DO3Apic and macropa, for these radionuclides. The 18-membered macrocycle, macropa, bound 132/135 La with better molar activity than DO3Apic under similar conditions. These chelators were conjugated to the prostate-specific membrane antigen (PSMA)-targeting agent DUPA to assess the use of radiolanthanum for in vivo imaging. The 132/135 La-labeled targeted constructs showed high uptake in tumor xenografts expressing PSMA. This study validates the use of these radioactive lanthanum isotopes for imaging applications and motivates future work to assess the therapeutic effects of the Auger electron emissions of 135 La.


Assuntos
Lantânio/química , Antígeno Prostático Específico/antagonistas & inibidores , Compostos Radiofarmacêuticos/química , Animais , Linhagem Celular Tumoral , Meios de Contraste/química , Compostos Heterocíclicos com 1 Anel/química , Humanos , Masculino , Camundongos , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Antígeno Prostático Específico/metabolismo , Neoplasias da Próstata/diagnóstico por imagem , Compostos Radiofarmacêuticos/metabolismo , Transplante Heterólogo
5.
Zhonghua Zhong Liu Za Zhi ; 41(11): 831-836, 2019 Nov 23.
Artigo em Chinês | MEDLINE | ID: mdl-31770850

RESUMO

Objective: To investigate the prognostic values of the maximum standardized uptake value (SUV(max)), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) calculated from pretreatment (18)F-fluorodeoxy glucose ((18)F-FDG) PET-CT results of patients with advanced extranodal NK/T cell lymphoma (ENKTL). Methods: The clinic data, follow-up data and pretreatment (18)F-FDG PET-CT data of 45 patients with ENKTL of stage Ⅳ were collected. The optimal cutoff value of progression-free survival (PFS) of SUV(max), MTV and TLG were analyzed by using receiver-operating characteristic (ROC) curve. The Kaplan-Meier method, Log-rank test and COX proportional hazards model were used for survival analysis, univariate analysis and multivariate analysis, respectively. Results: The median SUV(max), MTV and TLG of 45 ENKTL patients were 17.98, 70.18 and 755.42, respectively. ROC curve showed that the area under the curve (AUC) of SUV(max), MTV and TLG were 0.504 (P=0.970), 0.868 (P<0.001) and 0.848 (P=0.001), respectively. The value of SUV(max) was too small to fit for calculating the cutoff value of AUC. The cutoff value of MTV was 42.54 (sensitivity =78.1% and specificity =84.6%), and the cutoff value of TLG was 435.15 (sensitivity=75.0% and specificity =76.9%). Univariate analysis showed that lactate dehydrogenase (LDH) level, epstein-barr virus (EBV)-DNA, Eastern Cooperative Oncology Group (ECOG) score, bone marrow, Korean prognostic index (KPI), MTV, TLG were significantly related with PFS (all P<0.05), and lactate dehydrogenase (LDH) level, EBV-DNA, ECOG score, primary tumor location, KPI, MTV, TLG were significantly related with overall survival (OS) (all P<0.05). Multivariate analysis showed that KPI, MTV and TLG were independent prognostic predictors of PFS and OS (all P<0.05). Conclusions: MTV and TLG of pretreatment (18)F-FDG PET-CT are independent prognostic factors for PFS and OS of patients with advanced ENKTL. MTV and TLG may be more fit for evaluating the prognosis of ENKTL patients than SUV(max).


Assuntos
Linfoma Extranodal de Células T-NK/diagnóstico , Linfoma Extranodal de Células T-NK/metabolismo , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Fluordesoxiglucose F18/metabolismo , Glicólise , Humanos , Tomografia por Emissão de Pósitrons , Prognóstico , Intervalo Livre de Progressão , Compostos Radiofarmacêuticos/metabolismo , Estudos Retrospectivos , Análise de Sobrevida , Carga Tumoral
6.
BMC Cancer ; 19(1): 1000, 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31651282

RESUMO

BACKGROUNDS: Overexpression of epidermal growth factor receptor (EGFR) has been established as a valid therapeutic target of non-small cell lung cancer (NSCLC). However, the clinical benefit of cetuximab as an EGFR-targeting drug is still controversial, partially due to the lack of effective means to identify suitable patients. This study aimed to investigate the potential of radiolabeled cetuximab as a non-invasive tool to predict cetuximab accumulation in NSCLC tumor xenografts with varying EGFR expression levels. METHODS: The NSCLC tumors in model mice were subjected to in vivo biodistribution study and positron emission tomography (PET) imaging 48 h after injection of either 111In- or 64Cu-labeled cetuximab. The EGFR expression levels of NSCLC tumors were determined by ex vivo immunoblotting. RESULTS: We found that tumors with high EGFR expression had significantly higher [111In]In-DOTA-cetuximab accumulation than tumors with moderate to low EGFR expression (P < 0.05). Strong correlations were found between [111In]In-DOTA-cetuximab tumor uptake and EGFR expression level (r = 0.893), and between [64Cu]Cu-DOTA-cetuximab tumor uptake with EGFR expression level (r = 0.915). PET imaging with [64Cu]Cu-DOTA-cetuximab allowed clear visualization of tumors. CONCLUSION: Our findings suggest that this immuno-PET imaging can be clinically translated as a tool to predict cetuximab accumulation in NSCLC cancer patients prior to cetuximab therapy.


Assuntos
Antineoplásicos Imunológicos/metabolismo , Antineoplásicos Imunológicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cetuximab/metabolismo , Cetuximab/uso terapêutico , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/tratamento farmacológico , Tomografia por Emissão de Pósitrons/métodos , Animais , Antineoplásicos Imunológicos/química , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Cetuximab/química , Radioisótopos de Cobre/química , Radioisótopos de Cobre/metabolismo , Receptores ErbB/metabolismo , Feminino , Compostos Heterocíclicos com 1 Anel/química , Compostos Heterocíclicos com 1 Anel/metabolismo , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Compostos Radiofarmacêuticos/química , Compostos Radiofarmacêuticos/metabolismo , Distribuição Tecidual , Ensaios Antitumorais Modelo de Xenoenxerto
7.
Chem Commun (Camb) ; 55(86): 12932-12935, 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31599282

RESUMO

Here, we report the development of novel PET radiotracer ([11C]CW22) of BET proteins. In vivo imaging results in rodents and nonhuman primates (NHP) demonstrate that [11C]CW22 has excellent brain uptake, good specificity, good selectivity, suitable metabolism, appropriate kinetics and distribution in the brain. Our studies demonstrated that [11C]CW22 exhibits ideal properties as a PET imaging probe of BET proteins for further validation.


Assuntos
Encéfalo/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos/química , Animais , Barreira Hematotesticular/metabolismo , Encéfalo/metabolismo , Radioisótopos de Carbono/química , Cristalografia por Raios X , Cinética , Macaca , Camundongos , Conformação Molecular , Proteínas do Tecido Nervoso/química , Neurônios , Domínios Proteicos , Compostos Radiofarmacêuticos/metabolismo , Receptores de Superfície Celular/química
8.
Eur J Med Chem ; 183: 111730, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31563014

RESUMO

Designing novel 18F-labeled amino acid derivatives for targeted amino acid transporters is an attractive strategy for the development of therapeutic and diagnostic agents for cancer therapy. In this work, we have developed a novel 3-fluoropropyl analog of arginine, namely, (2S,4S)4-[18F]FPArg, [18F]1, to be used as a probe for studying arginine metabolism. Optically pure and labeled with 18F and 19F, (2S,4S)4-(3-fluoropropyl)arginine was synthesized and isolated in high radiochemical purity (>95%). In vitro uptake assays in human MCF-7 cells revealed that [18F]1 enters cells mainly via sodium-independent cationic amino acid transporters and was inhibited >62% by arginine. [18F]1 showed a high cellular uptake of 7.3 ±â€¯0.24% and 6.07 ±â€¯0.3% uptake/100 mg protein after incubation in MCF-7 and MDA-MB-231 cells for 120 min, respectively. In vivo biodistribution studies demonstrated that [18F]1 provided high tumor uptake and high tumor to muscle ratios (5:1 at the 30 and 60 min time points). In vivo PET imaging studies demonstrated tumor-specific uptake in nude mice bearing MCF-7 breast tumors with an excellent tumor-to-muscle ratio. These results suggest that [18F]1 is a promising tracer for clinical breast cancer imaging and may be used to diagnose and monitor diseases that are associated with arginine metabolism.


Assuntos
Arginina/análogos & derivados , Arginina/síntese química , Neoplasias da Mama/diagnóstico por imagem , Radioisótopos de Flúor/química , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos/síntese química , Animais , Arginina/metabolismo , Linhagem Celular Tumoral , Permeabilidade da Membrana Celular , Estabilidade de Medicamentos , Feminino , Humanos , Camundongos Nus , Estrutura Molecular , Compostos Radiofarmacêuticos/metabolismo , Relação Estrutura-Atividade , Distribuição Tecidual
9.
Int J Mol Sci ; 20(16)2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31412537

RESUMO

In this study, we synthesized a Zr-89-labeled anti-adenosine triphosphate synthase monoclonal antibody (ATPS mAb) for applications in immuno-positron emission tomography (PET) and evaluated its feasibility for angiogenesis imaging. The cellular uptake of Zr-89 ATPS mAb was measured after treatment of cancer cell lines in vitro, and its biodistribution was evaluated at 4, 24 and 48 h in vivo in mice bearing xenografts. PET images were acquired at 4, 24, 48, and 96 h after Zr-89 ATPS mAb administration. Tumor angiogenesis was analyzed using anti-CD31 immunofluorescence staining. The cellular uptake of Zr-89 ATPS mAb increased over time in MDA-MB-231 breast cancer cells but did not increase in PC3 prostate cancer cells. The tumor uptake of Zr-89 ATPS mAb at 24 h was 9.4 ± 0.9% ID/g for MDA-Mb-231 cells and was 3.8 ± 0.6% ID/g for PC3 cells (p = 0.004). Zr-89 ATPS mAb uptake in MDA-MB-231 xenografts was inhibited by the administration of cold ATPS mAb (4.4 ± 0.5% ID/g, p = 0.011). Zr-89 ATPS mAb uptake could be visualized by PET for up to 96 h in MDA-MB-231 tumors. In contrast, there was no distinct tumor uptake detected by PET in the PC3 xenograft model. CD31-positive tumor vessels were abundant in MDA-MB-231 tumors, whereas they were scarcely detected in PC3 tumors. In conclusion, ATPS mAb was successfully labeled with Zr-89, which could be used for immuno-PET imaging targeting tumor angiogenesis.


Assuntos
Trifosfato de Adenosina , Imagem Molecular , Neoplasias/diagnóstico por imagem , Neoplasias/patologia , Neovascularização Patológica/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Radioisótopos , Compostos Radiofarmacêuticos , Zircônio , Trifosfato de Adenosina/metabolismo , Animais , Anticorpos Monoclonais , Linhagem Celular Tumoral , Modelos Animais de Doenças , Feminino , Xenoenxertos , Humanos , Imunoconjugados , Masculino , Camundongos , Imagem Molecular/métodos , Tomografia por Emissão de Pósitrons/métodos , Radioisótopos/química , Radioisótopos/metabolismo , Compostos Radiofarmacêuticos/química , Compostos Radiofarmacêuticos/metabolismo , Distribuição Tecidual , Zircônio/química , Zircônio/metabolismo
10.
Pharm Res ; 36(10): 143, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31385111

RESUMO

PURPOSE: Pancreatic Polypeptide-secreting tumor of the distal pancreas (PPoma) is a rare, difficult and indolent type of cancer with a survival rate of 5-year in only 10% of all cases. The PPoma is classified as a neuroendocrine tumor (NET) not functioning that overexpresses SSTR 2 (somatostatin receptor subtype 2). Thus, in order to improve the diagnosis of this type of tumor, we developed nanoparticulate drug carriers based on poly-lactic acid (PLA) polymer loaded with octreotide and radiolabeled with Technetium-99 m (99mTc). METHODS: PLA/PVA octreotide nanoparticles were developed by double-emulsion technique. These nanoparticles were characterized by Atomic Force Microscopy (AFM) and Dynamic Light Scattering (DLS) and radiolabeled with 99mTc by the direct via forming 99mTc-PLA/PVA octreotide nanoparticles. The safety of these nanosystems was evaluated by the MTT cell toxicity assay and their in vivo biodistribution was evaluated in xenografted inducted animals. RESULTS: The results showed that a 189 nm sized nanoparticle were formed with a PDI of 0,097, corroborating the monodispersive behavior. These nanoparticles were successfully radiolabeled with 99mTc showing uptake by the inducted tumor. The MTT assay corroborated the safety of the nanosystem for the cells. CONCLUSION: The results support the use of this nanosystem (99mTc-PLA/PVA octreotide nanoparticles) as imaging agent for PPoma. Graphical Abstract Polypeptide-Secreting Tumor of the Distal Pancreas (PPoma) Radiolabeled Nanoparticles for Imaging.


Assuntos
Carcinoma Ductal Pancreático/diagnóstico por imagem , Nanopartículas/química , Octreotida/química , Neoplasias Pancreáticas/diagnóstico por imagem , Polipeptídeo Pancreático/metabolismo , Poliésteres/química , Compostos Radiofarmacêuticos/química , Tecnécio/química , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/metabolismo , Octreotida/metabolismo , Pâncreas/diagnóstico por imagem , Pâncreas/metabolismo , Neoplasias Pancreáticas/metabolismo , Tamanho da Partícula , Cintilografia/métodos , Compostos Radiofarmacêuticos/metabolismo , Receptores de Somatostatina/genética , Receptores de Somatostatina/metabolismo , Distribuição Tecidual
11.
J Cancer Res Ther ; 15(4): 842-848, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31436241

RESUMO

Aim: Tongue carcinoma is one of the most common oral and maxillofacial malignant tumors worldwide, maximum standardized uptake value (SUVmax) in 18 F-fluoro-2-deoxyglucose-positron emission tomography/computed tomography (PET/CT) has been widely used in cancer research; however, there are few systematical reports on the relationship between SUVmax and clinicopathological characteristics in tongue squamous cell carcinoma (TSCC). This study aimed to investigate the relationship between them and whether SUV parameters can predict lymph node metastasis. Materials and Methods: PET/CT manifestations and clinicopathological features of 52 patients with TSCC confirmed by pathology were retrospectively analyzed. Single-factor and multiple regression analyses were conducted on possible factors influencing TSCC SUVmax, including sex, age, smoking history, tumor location and size, histological differentiation, and tumor node metastasis (TNM) stages, T stages, and N stages. Diagnostic performance of SUVmax for lymph node metastasis was measured by the area under the receiver operating characteristic curve, and sensitivity and specificity were determined by Youden's J statistic. Results: SUVmax was correlated with sex, tumor location and size, and TNM stages, T stages, and N stages (P < 0.05) but was not correlated with histological differentiation, smoking history, and age (P > 0.05). Sex, tumor location, tumor size, and N stage were influencing factors independent of TSCC SUVmax (P < 0.05). TSCC SUVmax had predictive value for lymph node metastasis. When the cutoff value was 6.57, the diagnostic efficiency was the highest, with the sensitivity being 79.2% and the specificity being 85.7%. Conclusions: SUVmax was higher among male patients with TSCC with posterior tumor location, larger tumor size, and lymph node metastasis, and TSCC SUVmax was important in predicting lymph node metastasis.


Assuntos
Carcinoma de Células Escamosas/patologia , Fluordesoxiglucose F18/metabolismo , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos/metabolismo , Neoplasias da Língua/patologia , Adulto , Idoso , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/metabolismo , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Neoplasias da Língua/diagnóstico por imagem , Neoplasias da Língua/metabolismo , Adulto Jovem
12.
Nanoscale ; 11(28): 13243-13248, 2019 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-31290510

RESUMO

Here we report a two-step surface modification methodology to radiolabel small extracellular vesicles (SEVs) with 64CuCl2 for PET/MRI imaging. The modification did not change or damage the morphology, surface receptor proteins and internal RNA content. Radiolabeled SEVs could be detected in organs with low accumulation such as the brain (0.4-0.5% ID g-1) and their brain location determined by MRI.


Assuntos
Cobre/metabolismo , Vesículas Extracelulares/metabolismo , Imagem por Ressonância Magnética , Imagem Multimodal , Tomografia por Emissão de Pósitrons , Animais , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Cobre/química , Vesículas Extracelulares/química , Vesículas Extracelulares/ultraestrutura , Humanos , Camundongos , Compostos Radiofarmacêuticos/química , Compostos Radiofarmacêuticos/metabolismo
13.
Hell J Nucl Med ; 22(2): 131-134, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31273355

RESUMO

OBJECTIVE: Glutathione (GSH) plays an important role in a horde of cellular events that include cell proliferation and apoptosis.The present study describes the radio-synthesis and characterization of gallium-68 (68Ga)-labelled glutathione for its application in radionuclide imaging of cancer. SUBJECT AND METHODS: The radio-synthesis of radio-complex 68Ga-GSH was performed by the direct labeling method. The developed radio-complex was subjected to quality control tests. Colon tumors were developed in healthy male Sprague Dawley (S.D) rats by giving subcutaneous injections of dimethylhydrazine (DMH) in order to monitor the uptake of 68Ga-GSH radio-complex. RESULTS: Gallium-68-labelled glutathione was synthesized with a labeling efficiency of 73.5%±1%. Percentage plasma protein binding and log Po/w values for the radio-complex were found to be 20%-30% and -0.223±0.12, respectively. A significantly higher percentage specific uptake value of newly developed 68Ga-GSH complex was observed in colon tumor in comparison to soft tissue at 90 minutes post administration thereby exhibiting specificity for cancerous cells, which was also witnessed significantly increased overtime from the ratio of colon tumor uptake to normal colon uptake (P≤0.05). CONCLUSION: Therefore, 68Ga-labelled glutathione can further be exploited for radionuclide imaging and assessment of tumor drug resistance in patients.


Assuntos
Neoplasias do Colo/metabolismo , Radioisótopos de Gálio , Glutationa/química , Glutationa/metabolismo , Compostos Radiofarmacêuticos/química , Compostos Radiofarmacêuticos/metabolismo , Animais , Glutationa/farmacocinética , Marcação por Isótopo , Compostos Radiofarmacêuticos/farmacocinética , Ratos , Ratos Sprague-Dawley , Distribuição Tecidual
14.
Int J Clin Oncol ; 24(10): 1292-1300, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31165310

RESUMO

PURPOSE: The purpose of this study was to determine if quantitative SUV-related, volumetric FDG PET parameters, and texture features (SPs, VPs, and TFs, respectively) were useful to evaluate and predict response and recurrence after chemotherapy in follicular lymphoma (FL). METHODS: Pre- and posttreatment FDG PET examinations in 45 FL patients were analyzed retrospectively. In addition to SPs in the representative lesion, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were calculated as VPs for the representative and whole-body lesions. Six TFs were calculated in the pretreatment representative lesion. Response results with reduction of SPs or VPs after treatment (Δ) were compared to the Lugano classification based on visual assessment. SPs, VPs, and Δ of them as well as TFs were also evaluated if they allow prediction of response and recurrence after chemotherapy. RESULTS: Quantitative assessment with SPs and VPs provided 89% and 93-96% concordant results, respectively, with Lugano classification. Among pretreatment PET parameters, low gray-level zone emphasis (LGZE) in TFs solely showed statistical significance to predict complete response. All of posttreatment and Δ of SPs and VPs were considered as the predictors of progression free survival in the univariate Cox regression analysis, but none of them was the predictor in the multivariate analysis. CONCLUSION: This study demonstrated that quantitative PET parameters were applicable to evaluate treatment response in FL. Texture analysis showed promise in predicting treatment response. Although posttreatment and Δ of PET parameters were the candidates, all of them proved to have limited value in predicting recurrence after chemotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Fluordesoxiglucose F18/metabolismo , Linfoma Folicular/patologia , Recidiva Local de Neoplasia/patologia , Tomografia por Emissão de Pósitrons/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Linfoma Folicular/diagnóstico por imagem , Linfoma Folicular/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/tratamento farmacológico , Prognóstico , Compostos Radiofarmacêuticos/metabolismo , Estudos Retrospectivos , Carga Tumoral
15.
PLoS One ; 14(6): e0217781, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31206524

RESUMO

PURPOSE: Fluorodeoxyglucose-Positron-emission tomography (FDG-PET), quantified by standardized uptake values (SUV), is one of the most used functional imaging modality in clinical routine. It is widely acknowledged to be strongly associated with Glucose-transporter family (GLUT)-expression in tumors, which mediates the glucose uptake into cells. The present systematic review sought to elucidate the association between GLUT 1 and 3 expression with SUV values in various tumors. METHODS: MEDLINE library was screened for associations between FDG-PET parameters and GLUT correlation cancer up to October 2018. RESULTS: There were 53 studies comprising 2291 patients involving GLUT 1 expression and 11 studies comprising 405 patients of GLUT 3 expression. The pooled correlation coefficient for GLUT 1 was r = 0.46 (95% CI 0.40-0.52), for GLUT 3 was r = 0.35 (95%CI 0.24-0.46). Thereafter, subgroup analyses were performed. The highest correlation coefficient for GLUT 1 was found in pancreatic cancer r = 0.60 (95%CI 0.46-0.75), the lowest was identified in colorectal cancer with r = 0.21 (95% CI -0.57-0.09). CONCLUSION: An overall only moderate association was found between GLUT 1 expression and SUV values derived from FDG-PET. The correlation coefficient with GLUT 3 was weaker. Presumably, the underlying mechanisms of glucose hypermetabolism in tumors are more complex and not solely depended on the GLUT expression.


Assuntos
Proteínas Facilitadoras de Transporte de Glucose/metabolismo , Neoplasias/metabolismo , Compostos Radiofarmacêuticos/metabolismo , Animais , Fluordesoxiglucose F18/metabolismo , Humanos , Tomografia por Emissão de Pósitrons/métodos
16.
Eur J Med Chem ; 177: 291-301, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31158745

RESUMO

Based on our previous research on the fluorinated phenylquinoxaline scaffold, in this study, different positions of N,N-dimethyl amino group, and alkyl linkers with various lengths were introduced into this scaffold to regulate their lipophilicity and binding affinity to Tau. Four novel 99mTc/Re complexes with diethyl iminodiacetate chelator were synthesized and evaluated as Tau imaging tracers in the brain of Alzheimer's disease. Their specific binding to neurofibrillary tangles was verified by in vitro fluorescence staining and further confirmed by the results of immunofluorescence staining on the same brain sections from AD patient and Tg-tau mice. From in vitro binding assay using recombinant Tau aggregates, complex 4.2 with 6-N(CH3)2 and longer carbon chain (n = 4) displayed the highest affinity (Kd = 59.95 nM). [99mTc]4.2 was achieved by the ligand exchange reaction between dicarboxylic precursor and [99mTc(CO)3(H2O)3]+ intermediate with radiochemical yield over 45%. Ex vivo biodistribution studies on normal ICR mice revealed that [99mTc]4.2 exhibited moderate initial brain uptake (0.61% ID/g) and more structure optimizations are still required to improve the blood-brain barrier permeability.


Assuntos
Doença de Alzheimer/diagnóstico , Complexos de Coordenação/química , Corantes Fluorescentes/química , Compostos de Organotecnécio/química , Quinoxalinas/química , Proteínas tau/metabolismo , Idoso de 80 Anos ou mais , Peptídeos beta-Amiloides/metabolismo , Animais , Barreira Hematoencefálica/metabolismo , Encéfalo/metabolismo , Encéfalo/patologia , Quelantes/síntese química , Quelantes/química , Quelantes/metabolismo , Complexos de Coordenação/síntese química , Complexos de Coordenação/metabolismo , Feminino , Fluorescência , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/metabolismo , Humanos , Iminoácidos/síntese química , Iminoácidos/química , Iminoácidos/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Estrutura Molecular , Emaranhados Neurofibrilares/metabolismo , Emaranhados Neurofibrilares/patologia , Compostos de Organotecnécio/síntese química , Compostos de Organotecnécio/metabolismo , Fragmentos de Peptídeos/metabolismo , Quinoxalinas/síntese química , Quinoxalinas/metabolismo , Compostos Radiofarmacêuticos/síntese química , Compostos Radiofarmacêuticos/química , Compostos Radiofarmacêuticos/metabolismo , Rênio/química , Distribuição Tecidual
17.
Eur J Med Chem ; 177: 386-400, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31158752

RESUMO

We explored the approach of using an analog of E-64, a well-known and hydrophilic cysteine cathepsin (CC) inhibitor, as a potent cysteine cathepsin-trapping agent (CCTA) to improve the tumor retention of low-molecular-weight, receptor-targeted radiopharmaceuticals. The synthesized hydrophilic CCTA-incorporated, NTSR1-targeted agents demonstrated a substantial increase in cellular retention upon uptake into the NTRS1-positive HT-29 human colon cancer cell line. Similarly, biodistribution studies using HT-29 xenograft mice revealed a significant and substantial increase in tumor retention for the CCTA-incorporated, NTSR1-targeted agent. The intracellular trapping mechanism of the CCTA-incorporated agents by macromolecular adduct formation was confirmed using multiple in vitro and in vivo techniques. Furthermore, utilization of the more hydrophilic CCTA greatly increased the hydrophilicity of the resulting NTSR1-targeted constructs leading to substantial decreases in most non-target tissues in contrast to our previously reported dipeptidyl acyloxymethyl ketone (AOMK) constructs. This work further confirms that the CCTA trapping approach can make significant improvements in the clinical potential of NTSR1-and other receptor-targeted radiopharmaceuticals.


Assuntos
Catepsinas/antagonistas & inibidores , Inibidores Enzimáticos/metabolismo , Peptídeos/metabolismo , Compostos Radiofarmacêuticos/metabolismo , Receptores de Neurotensina/metabolismo , Animais , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Feminino , Células HT29 , Humanos , Interações Hidrofóbicas e Hidrofílicas , Lutécio/química , Camundongos SCID , Neoplasias/diagnóstico , Peptídeos/síntese química , Peptídeos/química , Radioisótopos/química , Compostos Radiofarmacêuticos/síntese química , Compostos Radiofarmacêuticos/química , Distribuição Tecidual
18.
Ren Fail ; 41(1): 467-472, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31162994

RESUMO

Introduction: To investigate the validity of the full age spectrum (FAS) equation in determining the glomerular filtration rate (GFR) in Chinese patients with chronic kidney disease (CKD) and to compare the performance of FAS equation and the technetium-99m-diethylene triamine pentaacetic acid (Tc-99m-DTPA) renal dynamic imaging method. Methods: The GFR was determined by three methods in the same day: (a) Tc-99m-DTPA dual plasma sample clearance method (mGFR); (b) FAS equation (eGFR1); (c) Tc-99m-DTPA renal dynamic imaging method (eGFR2). The mGFR was used as the reference standard. The Bland-Altman method, concordance correlation coefficient and regression equation were applied to evaluate the validity of the estimated glomerular filtration rate (eGFR). The bias, precision and accuracy were analyzed to compare the performances of eGFR1 and eGFR2. Results: A total of 162 subjects were enrolled in this study. The eGFR1 was correlated well with mGFR (concordance correlation coefficient was 0.896, p < 0.0001) and the regression equation was mGFR = -0.374 + 1.029eGFR1 (p < 0001). The Bland-Altman analysis proved good agreement between the eGFR1 and mGFR. In comparison with eGFR2, the eGFR1 showed better performance on bias (-1.22 vs. 8.92, p < 0001), precision (15.69 vs. 18.36, p = 0.047) and 30% accuracy (75.31% vs. 59.26%, p = 0.0009) in all participants. Conclusions: The FAS equation is valid in determining the glomerular filtration rate in Chinese patients with chronic kidney disease. The Tc-99m-DTPA renal dynamic imaging method is less accurate than the FAS equation and cannot be employed as the reference method in assessing the performance of FAS equation.


Assuntos
Taxa de Filtração Glomerular , Rim/fisiopatologia , Modelos Biológicos , Eliminação Renal/fisiologia , Insuficiência Renal Crônica/diagnóstico , Adulto , Fatores Etários , Idoso , Grupo com Ancestrais do Continente Asiático , Feminino , Humanos , Rim/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Compostos Radiofarmacêuticos/administração & dosagem , Compostos Radiofarmacêuticos/metabolismo , Insuficiência Renal Crônica/fisiopatologia , Pentetato de Tecnécio Tc 99m/administração & dosagem , Pentetato de Tecnécio Tc 99m/metabolismo , Tomografia Computadorizada de Emissão de Fóton Único
19.
Chemistry ; 25(45): 10698-10709, 2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31149749

RESUMO

Two structurally constrained chelators based on a fused bicyclic scaffold, 4-amino-4-methylperhydro-pyrido[1,2-a][1,4]diazepin-N,N',N'-triacetic acids [(4R*,10aS*)-PIDAZTA (L1) and (4R*,10aR*)-PIDAZTA (L2)], were designed for the preparation of GaIII -based radiopharmaceuticals. The stereochemistry of the ligand scaffold has a deep impact on the properties of the complexes, with unexpected [Ga(L2)OH] species being superior in terms of both thermodynamic stability and inertness. This peculiar behavior was rationalized on the basis of molecular modeling and appears to be related to a better fit in size of GaIII into the cavity of L2. Fast and efficient formation of the GaIII chelates at room temperature was observed at pH values between 7 and 8, which enables 68 Ga radiolabeling under truly physiological conditions (pH 7.4).


Assuntos
Compostos Bicíclicos com Pontes/química , Quelantes/química , Complexos de Coordenação/química , Complexos de Coordenação/síntese química , Complexos de Coordenação/metabolismo , Cristalografia por Raios X , Teoria da Densidade Funcional , Radioisótopos de Gálio/química , Meia-Vida , Humanos , Concentração de Íons de Hidrogênio , Cinética , Conformação Molecular , Compostos Radiofarmacêuticos/síntese química , Compostos Radiofarmacêuticos/química , Compostos Radiofarmacêuticos/metabolismo , Transferrina/química
20.
Radiat Oncol ; 14(1): 89, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31146757

RESUMO

BACKGROUND: Glioblastoma (GB) is the most common primary malignant brain tumor. Standard medical treatment consists of a maximal safe surgical resection, subsequently radiation therapy (RT) and chemotherapy with temozolomide (TMZ). An accurate definition of the tumor volume is of utmost importance for guiding RT. In this project we investigated the feasibility and treatment response of subvolume boosting to a PET-defined tumor part. METHOD: F98 GB cells inoculated in the rat brain were imaged using T2- and contrast-enhanced T1-weighted (T1w) MRI. A dose of 20 Gy (5 × 5 mm2) was delivered to the target volume delineated based on T1w MRI for three treatment groups. Two of those treatment groups received an additional radiation boost of 5 Gy (1 × 1 mm2) delivered to the region either with maximum [18F]FET or [18F]FAZA PET tracer uptake, respectively. All therapy groups received intraperitoneal (IP) injections of TMZ. Finally, a control group received no RT and only control IP injections. The average, minimum and maximum dose, as well as the D90-, D50- and D2- values were calculated for nine rats using both RT plans. To evaluate response to therapy, follow-up tumor volumes were delineated based on T1w MRI. RESULTS: When comparing the dose volume histograms, a significant difference was found exclusively between the D2-values. A significant difference in tumor growth was only found between active therapy and sham therapy respectively, while no significant differences were found when comparing the three treatment groups. CONCLUSION: In this study we showed the feasibility of PET guided subvolume boosting of F98 glioblastoma in rats. No evidence was found for a beneficial effect regarding tumor response. However, improvements for dose targeting in rodents and studies investigating new targeted drugs for GB treatment are mandatory.


Assuntos
Neoplasias Encefálicas/radioterapia , Modelos Animais de Doenças , Glioblastoma/radioterapia , Tomografia por Emissão de Pósitrons , Radioterapia Guiada por Imagem/métodos , Animais , Neoplasias Encefálicas/metabolismo , Linhagem Celular Tumoral , Estudos de Viabilidade , Feminino , Glioblastoma/metabolismo , Nitroimidazóis/metabolismo , Nitroimidazóis/uso terapêutico , Compostos Radiofarmacêuticos/metabolismo , Compostos Radiofarmacêuticos/uso terapêutico , Dosagem Radioterapêutica , Ratos Endogâmicos F344 , Resultado do Tratamento , Carga Tumoral , Tirosina/análogos & derivados , Tirosina/metabolismo , Tirosina/uso terapêutico
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