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2.
Chem Commun (Camb) ; 55(70): 10400-10403, 2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31402360

RESUMO

We report the first pretargeting in vivo study using the Strain-Promoted Sydnone-Alkyne Cycloaadition (SPSAC) reaction. The injection of a fluorine-18 labeled cyclooctyne three days after cetuximab bearing chlorosydnone moieties allowed a significant detection of the tumor by PET imaging suggesting an efficient click reaction inside the tumoral site. With a kinetic constant superior to 300 M-1 s-1, the SPSAC reaction might be an interesting tool, in addition to tetrazine-cyclooctene ligation, for in vivo chemistry.


Assuntos
Alquinos/química , Química Click/métodos , Radioisótopos de Flúor/química , Tomografia por Emissão de Pósitrons/métodos , Animais , Ciclização , Xenoenxertos , Humanos , Camundongos
3.
Bone Joint J ; 101-B(8): 910-914, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31362552

RESUMO

AIMS: Prosthetic joint infection (PJI) and aseptic loosening in total hip arthroplasty (THA) can present with pain and osteolysis. The Musculoskeletal Infection Society (MSIS) has provided criteria for the diagnosis of PJI. The aim of our study was to analyze the utility of F18-fluorodeoxyglucose (FDG) positron emission tomography (PET) CT scan in the preoperative diagnosis of septic loosening in THA, based on the current MSIS definition of prosthetic joint infection. PATIENTS AND METHODS: A total of 130 painful unilateral cemented THAs with a mean follow-up of 5.17 years (sd 1.12) were included in this prospective study. The mean patient age was 67.5 years (sd 4.85). Preoperative evaluation with inflammatory markers, aspiration, and an F18 FDG PET scan were performed. Diagnostic utility tests were also performed, based on the MSIS criteria for PJI and three samples positive on culture alone. RESULTS: The mean erythrocyte sedimentation rate, C-reactive protein, and white cell count were 47.83 mm/hr, 25.21 mg/l, and 11.05 × 109/l, respectively. The sensitivity, specificity, accuracy, negative predictive value, and false-positive rate of FDG PET compared with MSIS criteria were 94.87%, 38.46 %, 56.38%, 94.59 %, and 60.21%, respectively. The false-positive rate of FDG PET compared with culture alone was 77.4%. CONCLUSION: FDG PET has a definitive role in the preoperative evaluation of suspected PJI. This the first study to evaluate its utility based on MSIS criteria and compare it with microbiology results alone. However, FDG PET has a high false-positive rate. Therefore, we suggest that F18 FDG PET is useful in confirming the absence of infection, but if positive, may not be confirmatory of PJI. Cite this article: Bone Joint J 2019;101-B:910-914.


Assuntos
Fluordesoxiglucose F18 , Prótese de Quadril/efeitos adversos , Tomografia por Emissão de Pósitrons/métodos , Cuidados Pré-Operatórios/métodos , Infecções Relacionadas à Prótese/diagnóstico por imagem , Compostos Radiofarmacêuticos , Idoso , Reações Falso-Positivas , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Infecções Relacionadas à Prótese/cirurgia , Sensibilidade e Especificidade
4.
Cancer Radiother ; 23(6-7): 753-760, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31427076

RESUMO

Imaging provides the basis for radiotherapy. Multi-modality images are used for target delineation (primary tumor and nodes, boost volume) and organs at risk, treatment guidance, outcome prediction, and treatment assessment. Next to anatomical information, more and more functional imaging is being used. The current paper provides a brief overview of the different applications of imaging techniques used in the radiotherapy process, focusing on uncertainties and QA. The paper mainly focuses on PET and MRI, but also provides a short discussion on DCE-CT. A close collaboration between radiology, nuclear medicine and radiotherapy departments provides the key to improve the quality of radiotherapy. Jointly developed imaging protocols (RT position setup, immobilization tools, lasers, flat table…), and QA programs are mandatory. For PET, suitable windowing in consultation with a Nuclear Medicine Physician is crucial (differentiation benign/malignant lesions, artifacts…). A basic knowledge of MRI sequences is required, in such a way that geometrical distortions are easily recognized by all members the RT and RT physics team. If this is not the case, then the radiologist should be introduced systematically in the delineation process and multidisciplinary meetings need to be organized regularly. For each image modality and each image registration process, the associated uncertainties need to be determined and integrated in the PTV margin. When using functional information for dose painting, response assessment or outcome prediction, collaboration between the different departments is even more important. Limitations of imaging based biomarkers (specificity, sensitivity) should be known.


Assuntos
Imagem por Ressonância Magnética/métodos , Imagem Multimodal/métodos , Neoplasias/diagnóstico por imagem , Neoplasias/radioterapia , Garantia da Qualidade dos Cuidados de Saúde , Planejamento da Radioterapia Assistida por Computador/métodos , Incerteza , Artefatos , Humanos , Imagem por Ressonância Magnética/normas , Imagem Multimodal/normas , Estadiamento de Neoplasias , Neoplasias/patologia , Imagens de Fantasmas , Tomografia por Emissão de Pósitrons/métodos , Tomografia por Emissão de Pósitrons/normas , Tomografia Computadorizada por Raios X/métodos
5.
Cancer Radiother ; 23(6-7): 765-772, 2019 Oct.
Artigo em Francês | MEDLINE | ID: mdl-31451358

RESUMO

Image-guided brachytherapy is crucial in the management of locally advanced cervical cancers and has benefited from advances in imaging over recent decades. The recommendations of the European Brachytherapy - European Society for Radiation Oncology (GEC-ESTRO) have resulted in harmonized practices and improved clinical outcomes in terms of efficacy and toxicity. Post-implant magnetic resonance imaging (MRI) has become the reference imaging modality to guide brachytherapy. There is an increasing interest for other multimodal imaging in these patients. The metabolic information provided by Positrons Emission Tomography/computed tomodensitometry (PET/CT) is also very promising approach to guide personalized dose escalation strategies. The prognostic values of MRI and PET scanner before brachytherapy make it possible to consider personalizing the dose delivered in brachytherapy and to propose a dose escalation to patients who really need it and to possibly consider a deescalation strategy in patients with a very good prognosis. However, further studies are needed to confirm this approach.


Assuntos
Braquiterapia/métodos , Imagem por Ressonância Magnética Intervencionista/métodos , Imagem Multimodal/métodos , Órgãos em Risco/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Radioterapia Guiada por Imagem/métodos , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/radioterapia , Feminino , Humanos , Neoplasias do Colo do Útero/patologia
6.
Molecules ; 24(13)2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31288488

RESUMO

In this study, we have compared four 68Ga-labeled peptides (three Arg-Gly-Asp (RGD) peptides and substance-P) with two 18F-tracers clinically approved for tumor imaging. We have studied in vitro and in vivo characteristics of selected radiolabeled tracers in a glioblastoma multiforme tumor model. The in vitro part of the study was mainly focused on the evaluation of radiotracers stability under various conditions. We have also determined in vivo stability of studied 68Ga-radiotracers by analysis of murine urine collected at various time points after injection. The in vivo behavior of tested 68Ga-peptides was evaluated through ex vivo biodistribution studies and PET/CT imaging. The obtained data were compared with clinically used 18F-tracers. 68Ga-RGD peptides showed better imaging properties compared to 18F-tracers, i.e., higher tumor/background ratios and no accumulation in non-target organs except for excretory organs.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Radioisótopos de Gálio/química , Glioblastoma/diagnóstico por imagem , Oligopeptídeos/química , Compostos Radiofarmacêuticos/química , Animais , Neoplasias Encefálicas/metabolismo , Linhagem Celular Tumoral , Feminino , Radioisótopos de Flúor , Glioblastoma/metabolismo , Humanos , Camundongos SCID , Transplante de Neoplasias , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Tomografia por Emissão de Pósitrons/métodos , Distribuição Tecidual , Tomografia Computadorizada por Raios X
7.
Medicine (Baltimore) ; 98(29): e16509, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31335725

RESUMO

To evaluate the use of amyloid-positron emission tomography (PET) in routine clinical practice, in a selected population with cognitive impairment that meets appropriate use criteria (AUC).A multicenter, observational, prospective case-series study of 211patients from 2 level-3 hospitals who fulfilled clinical AUC for amyloid-PET scan in a naturalistic setting. Certainty degree was evaluated using a 5-point Likert scale: 0 (very low probability); 1 (low probability); 2 (intermediate probability); 3 (high probability); and 4 (practically sure), before and after amyloid PET. The treatment plan was considered as cognition-specific or noncognition-specific.Amyloid-PET was positive in 118 patients (55.9%) and negative in 93 patients (44.1%). Diagnostic prescan confidence according amyloid-PET results showed that in both, negative and positive-PET subgroup, the most frequent category was intermediate probability (45.7% and 55.1%, respectively). After the amyloid-PET, the diagnostic confidence showed a very different distribution, that was, in the negative-PET group the most frequent categories are very unlikely (70.7%) and unlikely (29.3%), while in the positive-PET group were very probable (57.6%) and practically sure (39%). Only in 14/211 patients (6.6%) the result of the amyloid-PET did not influence the diagnostic confidence, while in 194 patients (93.4%), the diagnostic confidence improved significantly after amyloid-PET results. The therapeutic intention was modified in 93 patients (44.1%). Specific treatment for Alzheimer disease was started, before amyloid-PET, in 80 patients (37.9%).This naturalistic study provides evidence that the implementation of amyloid-PET is associated with a significant improvement in diagnostic confidence and has a high impact on the therapeutic management of patients with mild cognitive impairment fulfilled clinical AUC.


Assuntos
Doença de Alzheimer/diagnóstico por imagem , Disfunção Cognitiva/diagnóstico por imagem , Placa Amiloide/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Idoso , Doença de Alzheimer/tratamento farmacológico , Disfunção Cognitiva/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
8.
J Comput Assist Tomogr ; 43(4): 664-670, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31259851

RESUMO

PURPOSE: To assess the diagnostic ability of whole-body magnetic resonance imaging (MRI) using integrated positron emission tomography/MRI(PET/MRI). METHODS: Axial T2-weighted image (T2WI), diffusion-weighted imaging (DWI), coronal T1-weighted image (T1WI), axial volumetric interpolated breath-hold examination in the lung field, and 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (FDG-PET) were evaluated in combination with T2WI alone, T2WI + DWI, T2WI + DWI + T1WI, T2WI + DWI + T1WI + volumetric interpolated breath-hold examination (all MRI images), and all MRI + FDG-PET. RESULTS: A total of 370 lesions were observed in 90 (62.5%) of the 144 patients. The lesion-based sensitivities were 62%, 74%, 74%, 76%, and 94%, and the patient-based sensitivities were 70%, 77%, 77%, 77%, and 81% using T2WI, T2WI + DWI, T2WI + DWI + T1WI, all MRI, and all MRI + FDG-PET, respectively. There were significant differences in the lesion-based sensitivity between T2WI and other sequence combinations and between all MRI and all MRI + FDG-PET. No significant differences were observed between any combinations among the patient-based sensitivities. CONCLUSION: The sensitivity of whole-body MRI was lower when lesion based, but almost equivalent when patient based compared with PET/MRI.


Assuntos
Imagem por Ressonância Magnética/métodos , Neoplasias/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Imagem Corporal Total/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Fluordesoxiglucose F18/uso terapêutico , Humanos , Interpretação de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Imagem Multimodal , Estudos Retrospectivos , Sensibilidade e Especificidade , Adulto Jovem
9.
Br J Radiol ; 92(1100): 20190247, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31166768

RESUMO

The myocardium and the cardiovascular system are often involved in patients with sarcoidosis. As therapy should be started as early as possible to avoid complications such as left ventricular dysfunction, a prompt and reliable diagnosis by means of non-invasive tests would be highly warranted. Among other techniques, 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) has emerged as a high sensitive tool to detect sites of inflammation before morphological changes are visible to conventional imaging techniques. We therefore aim at summarizing the most relevant findings in the literature on the use of 18F-fluorodeoxyglucose PET in the diagnostic workup of cardiac sarcoidosis and to underline future perspectives.


Assuntos
Cardiomiopatias/diagnóstico por imagem , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos , Sarcoidose/diagnóstico por imagem , Coração/diagnóstico por imagem , Humanos
10.
Anticancer Res ; 39(5): 2415-2427, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31092434

RESUMO

AIM: The purpose of this study was to develop a folate receptor-targeted 68Ga-labeled agent for the detection of cancer cells in mouse models of ovarian cancer by dual positron-emission tomography (PET) and magnetic resonance imaging (MRI). Moreover, we aimed to develop a controlled biopolymer-based chemistry that enables linking metal-binding (here Ga-68) chelators. MATERIALS AND METHODS: The nanoparticle (NP) agent was created by self-assembling of folic acid-modified polyglutamic acid and chelator-modified chitosan followed by radiolabeling with 68Ga (III) ions (68Ga-NODAGA-FA). The structure of modified biopolymers was characterized by spectroscopy. Particle size and mobility were determined. RESULTS: Significant selective binding of NPs was established in vitro using folate receptor-positive KB and - negative MDA-MB-231 cell lines. In vivo tumor uptake of folate-targeted 68Ga3+-radiolabeled NPs was tested using subcutaneous tumor-bearing CB17 SCID mice models. PET/MR dual modalities showed high tumor uptake with 6.5 tumor-to-muscle ratio and NP localization. CONCLUSION: In vivo results supporting the preliminary in vitro tests demonstrated considerably higher 68Ga-NODAGA-FA nanoparticle accumulation in KB tumors than in MDA-MB-231 tumors, thereby confirming the folate receptor-mediated uptake of this novel potential PET imaging agent.


Assuntos
Receptor 1 de Folato/isolamento & purificação , Radioisótopos de Gálio/química , Nanopartículas/química , Neoplasias Ovarianas/diagnóstico por imagem , Acetatos/química , Animais , Quelantes/química , Quitosana/síntese química , Quitosana/química , Quitosana/uso terapêutico , Modelos Animais de Doenças , Feminino , Receptor 1 de Folato/química , Ácido Fólico/química , Radioisótopos de Gálio/uso terapêutico , Compostos Heterocíclicos com 1 Anel/química , Humanos , Imagem por Ressonância Magnética/métodos , Camundongos , Nanopartículas/uso terapêutico , Neoplasias Ovarianas/patologia , Ácido Poliglutâmico/química , Tomografia por Emissão de Pósitrons/métodos
11.
Clin Nucl Med ; 44(7): 574-575, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31107747

RESUMO

For early-stage endometrial cancer patients who wish to preserve fertility, progestin treatment is effective. However, repeated endometrial curettage to evaluate treatment response may cause infertility. The clinical courses of 3 patients who were treated with fertility-sparing progestin treatment and underwent serial F-FES PET before and after treatment are presented. The SUVmean decreased greatly in patients with pathologically complete response (44.2%, 46.2%), whereas there was only a small change (22.5%) in the patient with pathologically stable disease who finally underwent hysterectomy. F-FES PET can be a noninvasive method to evaluate response to fertility-sparing progestin treatment.


Assuntos
Hiperplasia Endometrial/diagnóstico por imagem , Neoplasias do Endométrio/diagnóstico por imagem , Estradiol/análogos & derivados , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos , Adulto , Hiperplasia Endometrial/tratamento farmacológico , Neoplasias do Endométrio/tratamento farmacológico , Feminino , Humanos , Tomografia por Emissão de Pósitrons/normas , Progestinas/uso terapêutico
12.
Eur J Radiol ; 115: 46-52, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31084758

RESUMO

AIM: To examine the performance of 18F-FDG PET/MRI in the loco-regional staging of malignant pleural mesothelioma (MPM). METHODS: Consecutive subjects with MPM undergoing pre-operative staging with 18F-FDG PET/CT who underwent a same day integrated 18F-FDG PET/MRI were prospectively studied. Clinical TNM staging (AJCC 7th edition) was performed separately and in consensus by two readers on the 18F-FDG PET/MRI studies, and compared with staging by 18F-FDG PET/CT, and with final pathological stage, determined by a combination of intra-operative and histological findings. RESULTS: 10 subjects (9 male, mean age 68 years) with biopsy-proven MPM (9 epithelioid tumours, 1 biphasic) were included. One subject underwent neo-adjuvant chemotherapy between imaging and surgery and was excluded from the clinical versus pathological stage analysis. Pathological staging was concordant with staging by 18F-FDG PET/MRI in 67% (n = 6) of subjects, and with 18F-FDG PET/CT staging in 33% (n = 3). Pathological T stage was concordant with 18F-FDG PET/MRI in 78% (n = 7), and with 18F-FDG PET/CT in 33% (n = 3) of subjects. Pathological N stage was concordant with both 18F-FDG PET/MRI and 18F-FDG PET/CT in 78% (n = 7) of cases. No subject had metastatic disease. There was good inter-observer agreement for overall PET/MRI staging (weighted kappa 0.63) with moderate inter-reader agreement for T staging (weighted kappa 0.59). All 6 subjects with prior talc pleurodesis demonstrated mismatch between elevated FDG uptake and restricted diffusion in areas of visible talc deposition. CONCLUSION: Clinical MPM staging by 18F-FDG PET/MRI is feasible, and potentially provides more accurate loco-regional staging than PET/CT, particularly in T staging.


Assuntos
Neoplasias Pulmonares/patologia , Mesotelioma/patologia , Neoplasias Pleurais/patologia , Idoso , Biópsia , Feminino , Fluordesoxiglucose F18 , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Imagem Multimodal/métodos , Estadiamento de Neoplasias , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Tomografia por Emissão de Pósitrons/métodos , Estudos Prospectivos , Compostos Radiofarmacêuticos , Tomografia Computadorizada por Raios X/métodos
13.
Nat Methods ; 16(6): 526-532, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31086341

RESUMO

Glucose is a major source of energy for most living organisms, and its aberrant uptake is linked to many pathological conditions. However, our understanding of disease-associated glucose flux is limited owing to the lack of robust tools. To date, positron-emission tomography imaging remains the gold standard for measuring glucose uptake, and no optical tools exist for non-invasive longitudinal imaging of this important metabolite in in vivo settings. Here, we report the development of a bioluminescent glucose-uptake probe for real-time, non-invasive longitudinal imaging of glucose absorption both in vitro and in vivo. In addition, we demonstrate that the sensitivity of our method is comparable with that of commonly used 18F-FDG-positron-emission-tomography tracers and validate the bioluminescent glucose-uptake probe as a tool for the identification of new glucose transport inhibitors. The new imaging reagent enables a wide range of applications in the fields of metabolism and drug development.


Assuntos
Transportador de Glucose Tipo 1/fisiologia , Glucose/metabolismo , Neoplasias Experimentais/diagnóstico por imagem , Neoplasias Experimentais/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Animais , Transporte Biológico , Feminino , Fluordesoxiglucose F18/metabolismo , Humanos , Luciferases/metabolismo , Camundongos Knockout , Camundongos Nus , Neoplasias Experimentais/patologia , Compostos Radiofarmacêuticos/metabolismo , Células Tumorais Cultivadas
14.
BMC Infect Dis ; 19(1): 454, 2019 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-31117976

RESUMO

BACKGROUND: Mycolicibacterium phlei (M. phlei) is known to be a non-pathogenic nontuberculous mycobacterium (NTM) which rarely causes diseases in humans. A disseminated NTM infection is mostly caused by the Mycobacterium avium complex (MAC) and is known to develop in immunocompromised hosts, like those with acquired immune deficiency syndrome (AIDS). Here, we report a case of disseminated M. phlei infection in an immunocompetent host carrying anti-interferon gamma (IFN-γ) autoantibodies. CASE PRESENTATION: We detected M. phlei in multiple organs of an elderly woman with no significant medical history except positivity for anti-IFN-γ autoantibodies. She tested negative for human immunodeficiency virus (HIV)-1, 2/ Human T-cell leukemia virus type 1 (HTLV-1) antibody. High-resolution computed tomography (HRCT) of the chest demonstrated a nodule in the left S1 + 2 segment, interlobular septal thickening, multi lymphadenopathy, and osteolysis. A maximum intensity projection image following fluorodeoxyglucose-positron emission tomography (FDG-PET) revealed multifocal hypermetabolic lesions in the nodule and all the swollen lymph nodes seen in HRCT. FDG also accumulated in multiple bones. Advanced primary lung cancer was suspected, and biopsies of each lesion were performed. The pathology revealed caseating granuloma, positive for acid-fast bacteria, and DNA sequencing of the acid-fast bacteria confirmed the organism to be M. phlei. The patient also tested positive for anti-IFN-γ autoantibodies. Based on these findings, she was diagnosed with disseminated M. phlei infection, with anti-IFN-γ autoantibodies. CONCLUSIONS: Though known to be non-pathogenic, we show that M. phlei can be pathogenic like the MAC in immunocompetent individuals carrying anti-IFN-γ autoantibodies.


Assuntos
Interferon gama/imunologia , Infecções por Micobactéria não Tuberculosa/imunologia , Micobactérias não Tuberculosas/patogenicidade , Idoso , Antibacterianos/uso terapêutico , Autoanticorpos , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/patologia , Feminino , Granuloma/diagnóstico por imagem , Granuloma/tratamento farmacológico , Granuloma/microbiologia , Humanos , Imunocompetência , Infecções por Micobactéria não Tuberculosa/diagnóstico por imagem , Infecções por Micobactéria não Tuberculosa/tratamento farmacológico , Infecções por Micobactéria não Tuberculosa/microbiologia , Micobactérias não Tuberculosas/imunologia , Tomografia por Emissão de Pósitrons/métodos , Tomografia Computadorizada por Raios X/métodos , Virulência
15.
Eur J Med Chem ; 176: 410-418, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31125895

RESUMO

Positron emission tomography (PET) imaging of the 18 kDa translocator protein (TSPO), has a high diagnostic potential in neurodegenerative disorders and cancer. However, TSPO is considered a challenge for molecular imaging due to the poor availability of suitable radiotracers with adequate pharmacokinetic properties. Here, we describe the development of a radiofluorinated pyridinyl isoquinoline analogue of the established TSPO PET tracer (R)-[11C]PK11195 with improved binding properties in all known human TSPO phenotypes. We conducted a complete preclinical evaluation using in vitro, in vivo and ex vivo methods to assess the performance of this novel radiotracer and observed high specific binding of the radiotracer to TSPO, as well as high metabolic stability. Therefore, we propose this radiolabeled compound for further evaluation in animal models as well as in clinical trials.


Assuntos
Isoquinolinas/metabolismo , Piridinas/metabolismo , Compostos Radiofarmacêuticos/metabolismo , Receptores de GABA/metabolismo , Animais , Feminino , Radioisótopos de Flúor/química , Humanos , Isoquinolinas/síntese química , Isoquinolinas/química , Isoquinolinas/farmacocinética , Marcação por Isótopo , Camundongos Endogâmicos C57BL , Microssomos Hepáticos/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Piridinas/síntese química , Piridinas/química , Piridinas/farmacocinética , Compostos Radiofarmacêuticos/síntese química , Compostos Radiofarmacêuticos/química , Compostos Radiofarmacêuticos/farmacocinética , Distribuição Tecidual
16.
Eur J Med Chem ; 176: 129-134, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31102933

RESUMO

Cardiovascular disease is the leading cause of mortality and morbidity worldwide. Atherosclerosis accounts for 50% of deaths in western countries. This multifactorial pathology is characterized by the accumulation of lipids and inflammatory cells within the vascular wall, leading to plaque formation. We describe herein the synthesis of a PCTA-based 68Ga3+ chelator coupled to a phospholipid biovector 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE), which is the main constituent of the phospholipid moiety of High-Density Lipoprotein (HDL) phospholipid moiety. The resulting 68Ga-PCTA-DSPE inserted into HDL particles was compared to 18F-FDG as a PET agent to visualize atherosclerotic plaques. Our agent markedly accumulated within mouse atheromatous aortas and more interestingly in human endarterectomy carotid samples. These results support the potential use of 68Ga-PCTA-DSPE-HDL for atherosclerosis PET imaging.


Assuntos
Aterosclerose/diagnóstico por imagem , Quelantes/química , Radioisótopos de Gálio/química , Compostos Heterocíclicos com 2 Anéis/química , Fosfatidiletanolaminas/química , Compostos Radiofarmacêuticos/química , Animais , Aorta/metabolismo , Aorta/patologia , Apolipoproteínas E/genética , Artérias Carótidas/metabolismo , Artérias Carótidas/patologia , Quelantes/síntese química , Portadores de Fármacos/química , Desenvolvimento de Medicamentos , Compostos Heterocíclicos com 2 Anéis/síntese química , Humanos , Lipoproteínas HDL/química , Fígado/metabolismo , Camundongos Knockout , Miocárdio/metabolismo , Miocárdio/patologia , Fosfatidiletanolaminas/síntese química , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos/síntese química
17.
Intern Med ; 58(8): 1167-1172, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30982805

RESUMO

Hashimoto's encephalopathy (HE) is a steroid-responsive autoimmune encephalopathy associated with Hashimoto thyroiditis. We herein report a case of HE manifesting "smoldering" limbic encephalitis with persisting symptoms and abnormalities on examinations. Although our patient experienced partial clinical remission after treatment, hippocampal hypermetabolism on [18F] fluorodeoxyglucose positron emission tomography (FDG-PET) and subclinical seizures on video electroencephalography persisted. Hypermetabolism on FDG-PET was improved by additional prednisolone therapy. Thus, as with other autoimmune limbic encephalitis cases, HE can take a course of "smoldering" encephalitis. FDG-PET and electroencephalogram findings can reflect the disease activity degree in such patients, although with certain neurophysiological and biochemical distinctions.


Assuntos
Doenças Autoimunes/fisiopatologia , Encefalite/fisiopatologia , Doença de Hashimoto/fisiopatologia , Encefalite Límbica/fisiopatologia , Idoso , Doenças Autoimunes/diagnóstico , Biomarcadores/análise , Eletroencefalografia/métodos , Encefalite/diagnóstico , Feminino , Doença de Hashimoto/diagnóstico , Humanos , Encefalite Límbica/complicações , Encefalite Límbica/diagnóstico , Tomografia por Emissão de Pósitrons/métodos
18.
Clin Nucl Med ; 44(5): 401-403, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30932973

RESUMO

Ac-based PSMA-targeted therapy has emerged as promising agent for the treatment of metastatic castration-resistant prostate cancer. Posttherapy image is used for tracer localization and dosimetry. Prior 2 photopeaks of 440 and 218 KeV were reported for posttherapy imaging. Our study of gamma ray spectrum, phantom, and clinical images show that imaging with 3 major photopeaks of 78, 218, and 440 KeV gives better quality images, high count statistics, and higher number of lesion delineations. It is therefore suggested that posttherapy imaging may be carried out using 3 major abundant photopeaks.


Assuntos
Actínio/farmacocinética , Dipeptídeos/farmacocinética , Compostos Heterocíclicos com 1 Anel/farmacocinética , Tomografia por Emissão de Pósitrons/métodos , Neoplasias de Próstata Resistentes à Castração/diagnóstico por imagem , Compostos Radiofarmacêuticos/farmacocinética , Actínio/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons/normas , Neoplasias de Próstata Resistentes à Castração/radioterapia , Radiometria/métodos , Radiometria/normas , Compostos Radiofarmacêuticos/uso terapêutico , Padrões de Referência
20.
Technol Cancer Res Treat ; 18: 1533033819841066, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30929606

RESUMO

INTRODUCTION: Glucose utilization and lactate release are 2 important indicators of cancer metabolism. Most tumors consume glucose and release lactate at a higher rate than normal tissues due to enhanced aerobic glycolysis. However, these 2 indicators of metabolism have not previously been studied on a single-cell level, in the same cell. OBJECTIVE: To develop and characterize a novel droplet microfluidic device for multiplexed measurements of glucose uptake (via its analog 18F-fluorodeoxyglucose) and lactate release, in single live cells encapsulated in an array of water-in-oil droplets. RESULTS: Surprisingly, 18F-fluorodeoxyglucose uptake and lactate release were only marginally correlated at the single-cell level, even when assayed in a standard cell line (MDA-MB-231). While 18F-fluorodeoxyglucose-avid cells released substantial amounts of lactate, the reverse was not true, and many cells released high amounts of lactate without taking up 18F-fluorodeoxyglucose. DISCUSSION: These results confirm that cancer cells rely on multiple metabolic pathways in addition to aerobic glycolysis and that the use of these pathways is highly heterogeneous, even under controlled culture conditions. Clinically, the large cell-to-cell variability suggests that positron emission tomography measurements of 18F-fluorodeoxyglucose uptake represent metabolic flux only in an aggregate sense, not for individual cancer cells within the tumor.


Assuntos
Neoplasias da Mama/patologia , Fluordesoxiglucose F18/metabolismo , Ácido Láctico/metabolismo , Microfluídica/instrumentação , Microfluídica/métodos , Compostos Radiofarmacêuticos/metabolismo , Análise de Célula Única/métodos , Transporte Biológico , Neoplasias da Mama/metabolismo , Feminino , Humanos , Tomografia por Emissão de Pósitrons/métodos , Células Tumorais Cultivadas
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