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1.
AJR Am J Roentgenol ; 214(4): 908-916, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32069078

RESUMO

OBJECTIVE. The purpose of this study is to evaluate the prognostic value of quantitative metabolic parameters from pretreatment PET/CT scans of patients with squamous cell cervical cancer. MATERIALS AND METHODS. This retrospective study included 120 patients with biopsy-proven squamous cell carcinoma of the cervix who underwent FDG PET/CT for initial tumor staging. The primary tumor maximum standardized uptake value (SUVmax) and mean standardized uptake value (SUVmean), tumor glycolytic activity, metabolic tumor volume (MTV), and metabolic intratumoral heterogeneity index (calculated as the AUC for the cumulative standardized uptake value [SUV]-volume histogram [CSH] index) were obtained. Information on patient demographic characteristics and tumor staging were collected. Median follow-up was 27.5 months. Overall survival (OS) and progression-free survival (PFS) were calculated using a multivariate Cox proportional hazards regression model and log-rank (Mantel-Cox) test to generate Kaplan-Meier survival plots. RESULTS. The mean (± SD) age of the patients was 54.4 ± 13.1 years. Twenty-two patients had stage I disease; 58, stage II; 23, stage III; and 17, stage IV. Thirty-three patients died, 82 were living, and five were lost to follow-up and were censored; 29 patients had disease progression. The median survival was 74.9 months (95% CI, 63.6-86.9 months). A higher MTV was significantly associated with reduced OS in multivariate analysis (hazard ratio, 1.085; 95% CI, 1.036-1.136; p = 0.0005). A higher AUC-CSH index (denoting lower tumor heterogeneity) was significantly associated with increased OS (hazard ratio, 0.662; 95% CI, 0.448-0.979; p = 0.04) and PFS (hazard ratio, 0.683; 95% CI, 0.471-0.991; p = 0.045) in multivariate analysis. Kaplan-Meier survival analysis using the median value for MTV (61 mL) significantly predicted OS (p = 0.0009). CONCLUSION. Tumor heterogeneity on pretreatment PET/CT is associated with OS and PFS in patients with cervical cancer. MTV is significantly associated with OS.


Assuntos
Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/metabolismo , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Fluordesoxiglucose F18/farmacocinética , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Compostos Radiofarmacêuticos/farmacocinética , Estudos Retrospectivos , Taxa de Sobrevida , Carga Tumoral , Neoplasias do Colo do Útero/mortalidade
2.
Inorg Chem ; 59(3): 1985-1995, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-31976659

RESUMO

44Sc is an attractive positron-emitting radionuclide for PET imaging; herein, a new complex of the Sc3+ ion with nonmacrocyclic chelator H4pypa was synthesized and characterized with high-resolution electrospray-ionization mass spectrometry (HR-ESI-MS), as well as different nuclear magnetic resonance (NMR) spectroscopic techniques (1H, 13C, 1H-13C HSQC, 1H-13C HMBC, COSY, and NOESY). In aqueous solution (pH = 7), [Sc(pypa)]- presented two isomeric forms, the structures of which were predicted using density functional theory (DFT) calculation with a small energy difference of 22.4 kJ/mol, explaining their coexistence. [Sc(pypa)]- was found to have superior thermodynamic stability (pM = 27.1) compared to [Sc(AAZTA)]- (24.7) and [Sc(DOTA)]- (23.9). In radiolabeling, [44Sc][Sc(pypa)]- formed efficiently at RT in 15 min over a range of pH (2-5.5), resulting in a complex that is highly stable (>99%) in mouse serum over at least six half-lives of scandium-44. Similar labeling efficiency was observed with the PSMA (prostate-specific membrane antigen)-targeting H4pypa-C7-PSMA617 at pH = 5.5 (RT, 15 min), confirming negligible disturbance from the bifunctionalization on scandium-44 scavenging. Moreover, the kinetic inertness of the radiocomplex was proved in vivo. Surprisingly, the molar activity was found to have profound influence on the pharmacokinetics of the radiotracers where lower molar activity drastically reduced the background accumulations, particularly, kidney, and thus, yielded a much higher tumor-to-background contrast.


Assuntos
Quelantes/química , Complexos de Coordenação/química , Neoplasias Experimentais/diagnóstico por imagem , Antígeno Prostático Específico/análise , Radioisótopos/química , Compostos Radiofarmacêuticos/química , Escândio/química , Termodinâmica , Animais , Quelantes/síntese química , Quelantes/farmacocinética , Complexos de Coordenação/síntese química , Complexos de Coordenação/farmacocinética , Teoria da Densidade Funcional , Humanos , Concentração de Íons de Hidrogênio , Camundongos , Camundongos Nus , Modelos Moleculares , Estrutura Molecular , Tomografia por Emissão de Pósitrons , Radioisótopos/farmacocinética , Compostos Radiofarmacêuticos/síntese química , Compostos Radiofarmacêuticos/farmacocinética , Escândio/farmacocinética , Distribuição Tecidual
3.
Metabolism ; 104: 154168, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31982479

RESUMO

BACKGROUND: There is no consensus in the field regarding the optimal method for the expression of metabolic flux data, such as glucose disposal rates during hyperinsulinemic-euglycemic clamp experiments. Several normalization methods are in use today, but their impact on study outcomes is rarely discussed. METHODS: We illustrate this issue using clamp data from 92 lean and 66 obese subjects. Glucose kinetics and insulin sensitivity were determined during hyperinsulinemic-euglycemic clamp studies using [6,6-2H2]glucose. From this single dataset, we calculated 21 expression methods for the glucose disposal rate during hyperinsulinemic conditions. RESULTS AND DISCUSSION: With most normalization methods, the obese subjects demonstrated reduced insulin-stimulated glucose disposal as compared to the lean subjects. However, depending on the normalization method, glucose disposal rates in obese subjects ranged from 26 ±â€¯1% to 207 ±â€¯10% of glucose disposal rates in lean subjects. We conclude that data normalization methods greatly impacted metabolic flux outcomes in our dataset of lean and obese subjects. There is no compelling evidence to select one method over the other, but we encourage authors in the metabolic arena to think about, and provide a rationale for, the best normalization method for their specific research questions.


Assuntos
Técnica Clamp de Glucose/estatística & dados numéricos , Técnica Clamp de Glucose/normas , Metabolismo/fisiologia , Bases de Dados Factuais , Glucose/metabolismo , Humanos , Resistência à Insulina , Cinética , Obesidade/metabolismo , Compostos Radiofarmacêuticos/farmacocinética , Valores de Referência
4.
Eur J Pharm Sci ; 141: 105112, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31629917

RESUMO

Breast cancer is the most common type of cancer in women worldwide. There have been many efforts for early breast cancer detection and among them molecular imaging have been extremely of high importance. Single-photon emission computed tomography (SPECT/CT) is a kind of imaging technique able to reveal crucial information with using radiopharmaceuticals. In this study, Technetium-99m-(DOTA-NHS-ester)-Methionine radiopharmaceutical was synthesized. Between 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic acid mono-N-hydroxysuccinimide ester (DOTA-HNS ester) (MACROCYCLICS, DOTA-NHS ester, Plano, Texas, USA) and methionine(marker) were conjugated. The DOTA-HNS ester-Methionine was labeled with Technetium-99m (Inter-Medical, Technetium-99m, Bergamo, Italy). The synthesized radiopharmaceutical was used in SPECT/CT imaging for breast cancer diagnosis. For radiopharmaceutical evaluation, MTT assay for cellular toxicity, biodistribution, cellular uptake and radiochemical purity were employed.Technetium-99m-(DOTA-NHS-ester)-Methionine radiochemical had less cellular toxicity in human embryonic kidney cells 293 cell line (HEK293). Cellular uptake was indicated higher percent with use of Methionine as a marker, and radiochemical purity was high. Based on the results Technetium-99m-(DOTA-NHS-ester)-Methionine radiochem may be a better option for early detection of breast cancer. Further study is recommended to confirm these findings in clinical practice.


Assuntos
Meios de Contraste/administração & dosagem , Metionina/administração & dosagem , Compostos Radiofarmacêuticos/administração & dosagem , Succinimidas/administração & dosagem , Tecnécio/administração & dosagem , Animais , Transporte Biológico , Sobrevivência Celular/efeitos dos fármacos , Meios de Contraste/farmacocinética , Ésteres , Células HEK293 , Humanos , Células MCF-7 , Masculino , Metionina/farmacocinética , Camundongos , Neoplasias/metabolismo , Compostos Radiofarmacêuticos/farmacocinética , Succinimidas/farmacocinética , Tecnécio/farmacocinética , Distribuição Tecidual , Tomografia Computadorizada de Emissão de Fóton Único
5.
Curr Radiopharm ; 12(3): 211-219, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31612808

RESUMO

BACKGROUND: Nephrotoxicity is a prevalent consequence of cancer treatment using radiotherapy and chemotherapy or their combination. There are two methods; histological and biochemical, to assess the kidney damage caused by toxic agents in animal studies. Although these methods are used for the try-out of renoprotective factors, these methods are invasive and time-consuming, and also, lack the necessary sensitivity for primary diagnosis. Quantitative renal 99mTc-DMSA scintigraphy is a noninvasive, precise and sensitive radionuclide technique which is used to assess the extent of kidney damage, so that the extent of injury to the kidney will be indicated by the renal uptake rate of 99mTc-DMSA in the kidney. In addition, this scintigraphy evaluates the effect of the toxic agents by quantifying the alterations in the biodistribution of the radiopharmaceutical. CONCLUSION: In this review, the recent findings about the renoprotective agents were evaluated and screened with respect to the use of 99mTc-DMSA , which is preclinically and clinically used for animal cases and cancer patients under the treatment by radiotherapy and chemotherapy.


Assuntos
Neoplasias Renais/metabolismo , Rim/metabolismo , Substâncias Protetoras/farmacocinética , Compostos Radiofarmacêuticos/farmacocinética , Ácido Dimercaptossuccínico Tecnécio Tc 99m/farmacocinética , Animais , Humanos , Rim/diagnóstico por imagem , Rim/efeitos dos fármacos , Rim/efeitos da radiação , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/radioterapia , Cintilografia
6.
Br J Radiol ; 92(1104): 20190380, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31600089

RESUMO

OBJECTIVE: To evaluate the therapeutic response, progression free survival (PFS), overall survival (OS) and clinical toxicity of 177Lu-PSMA-617 PSMA targeted radioligand therapy (PRLT) in the setting of heavily pre-treated metastatic castrate-resistant prostate cancer (mCPRC) patients and also examine the association of prognostic variables with therapeutic outcome in such patient cohort. METHODS: We examined the medical records of mCRPC patients who had undergone 177Lu-PSMA-617 PRLT from March 2017 to February 2019 in our institute. Patients receiving equal to or more than two cycles were included and analyzed in this retroprospective study.The 68Ga-PSMA-11 PET-CT and 18-fludeoxyglucose positron emission tomography (18FDG PET)-CT scan findings, serum prostate-specific antigen (PSA) change, health-related quality of life (HRQoL) scales (Eastern Cooperative Oncology Group/Karnofsky score) and Gleason score were assessed for their implications on the outcome of therapy. The treatment response was evaluated under three categories: (a) symptomatic (b) biochemical and (c) imaging response.The PFS and OS following first PRLT were determined and the association of various variables with PSA doubling time (DT) and FDG uptake in the lesions were analyzed. Toxicity assessment was undertaken objectively by National Cancer Institute-Common Terminology Criteria for Adverse Events scale v. 5.0 for haematological and nephrotoxicity, and salivary gland toxicity assessed by xerostomia inventory score. RESULTS: A total of 40 mCRPC patients (age range: 46-84 years; median 63 years), who had undergone 177Lu-PSMA-617 PRLT, of at least two cycles was identified and selected for the analysis. FDG uptake was noted in 87.5% of patients (n = 35). Out of 40 cases, 21 were responders (CR, PR and SD) and 19 were non-responders (PD) on symptomatic and biochemical scales while on molecular imaging response, 16 (43%) were responders and remaining 21 (57%) were non-responders. Lesion-wise, 68Ga-PSMA-11 avid metastatic nodal disease responded well with 177Lu PSMA-617 PRLT, as compared to hepatic and skeletal lesions. The median OS and PFS was 12 and 7 months respectively following first PRLT. Patients with negative serum PSA-DT demonstrated superior 1 year PFS as compared to those with positive serum PSA-DT (52.5 vs 47.5%) (p = 0.029). Patients receiving greater than two cycles PRLT demonstrated a higher negative PSA-DT as compared to those receiving two cycles (p-value = 0.03). Grade 1 xerostomia was observed in two patients (5%) (mean xerostomia score of 23), haematotoxicity in seven patients [Grade I (n = 2, 5%) and Grade II (n = 5, 14%)]. CONCLUSION: 177Lu-PSMA-617 PRLT was well-tolerated and able to produce disease control with good symptomatic and biochemical responses in the context of heavily pre-treated mCRPC with progressive disease, with low toxicity profile. Evident association of high FDG uptake was observed with aggressive disease biology coupled with increasing Gleason score and poorer 12 months PFS. Negative PSA-DT following therapy demonstrated longer PFS. The results demonstrate important future role of 177Lu-PSMA-617 PRLT in the treatment of mCRPC. ADVANCES IN KNOWLEDGE: The present work explored in a large teriary cancer care setting, the efficacy of 177Lu-PSMA-617 PRLT, in an aggressive and unselected subset of mCRPC. The response and outcome was correlated with a number of prognostic variables, including molecular imaging findings (FDG uptake in the metastatic lesions), PSA DT and Gleason score.


Assuntos
Dipeptídeos/uso terapêutico , Fluordesoxiglucose F18/farmacocinética , Glutamato Carboxipeptidase II/antagonistas & inibidores , Compostos Heterocíclicos com 1 Anel/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/metabolismo , Compostos Radiofarmacêuticos/farmacocinética , Idoso , Idoso de 80 Anos ou mais , Antígenos de Superfície , Dipeptídeos/efeitos adversos , Radioisótopos de Gálio/uso terapêutico , Compostos Heterocíclicos com 1 Anel/efeitos adversos , Humanos , Lutécio/uso terapêutico , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular/métodos , Gradação de Tumores , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Prognóstico , Intervalo Livre de Progressão , Antígeno Prostático Específico/sangue , Neoplasias de Próstata Resistentes à Castração/mortalidade , Neoplasias de Próstata Resistentes à Castração/patologia , Qualidade de Vida , Radioisótopos/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento
7.
Molecules ; 24(17)2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31470531

RESUMO

The human epidermal growth factor receptor 2 (HER2) represents one of the most studied tumor-associated antigens for cancer immunotherapy. The receptors for HER2 are overexpressed in various human cancers, such as breast and ovarian cancer. The relatively low expression of this antigen on normal tissues makes it a clinically useful molecular target for tumor imaging and targeted therapy. HER2 overexpression is correlated with aggressive tumor behavior and poor clinical outcomes. Thus, HER2 has become an important prognostic and predictive factor, as well as a potential molecular target. Due to the heterogeneity of breast cancer and possible discordance in HER2 status between primary tumors and distant metastases, assessment of HER2 expression by noninvasive imaging is important. Molecular imaging of HER2 expression may provide essential prognostic and predictive information concerning disseminated cancer and aid in the selection of an optimal therapy. Another tumor-specific antigen is MUC1, which is silent on normal tissues, but overexpressed in almost all human epithelial cell cancers, including >90% of human breast, ovarian, pancreatic, colorectal, lung, prostate, and gastric cancers and is a promising tumor antigen with diagnostic as well as the therapeutic potential of cancer. Radiolabeled small peptide ligands are attractive as probes for molecular imaging, as they reach and bind the target receptor efficiently and clear from blood and non-target organs faster than bulky antibodies. In this study, HER2 and MUC1-based peptides were synthesized and preclinically evaluated in an effort to develop peptide-based SPECT radiopharmaceuticals derived from tumor-associated antigens for the detection of breast cancer. Our findings demonstrate that the tumor antigen peptides radiolabeled efficiently with 99mTc and showed high metabolic stability in human plasma in vitro. The data from breast tumor cell binding confirmed the high affinity (in low nanomolar range) towards respective breast cancer cell lines. In healthy mice, 99mTc-labeled peptides displayed favorable pharmacokinetics, with high excretion by the renal system. In tumor xenografts nude mice models, good uptake by the SKBR3, MCF7, and T47D tumors were found, with good tumor-to-blood and tumor to muscle ratios. Additionally, tumor lesions can be seen in γ-camera imaging. Our data suggest that based on its ability to detect HER2- and MUC1-positive breast cancer cells in vivo, 99mTc-HER2 and 99mTc-MUC1-targeted peptides may be promising tumor imaging probes and warrant further investigation.


Assuntos
Antígenos de Neoplasias/metabolismo , Neoplasias da Mama/diagnóstico por imagem , Mucina-1/metabolismo , Peptídeos/síntese química , Receptor ErbB-2/metabolismo , Animais , Antígenos de Neoplasias/genética , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Feminino , Expressão Gênica , Xenoenxertos , Humanos , Células MCF-7 , Camundongos , Camundongos Nus , Imagem Molecular/métodos , Mucina-1/genética , Peptídeos/metabolismo , Peptídeos/farmacocinética , Ligação Proteica , Compostos Radiofarmacêuticos/química , Compostos Radiofarmacêuticos/farmacocinética , Receptor ErbB-2/genética , Técnicas de Síntese em Fase Sólida/métodos , Tecnécio/química , Tecnécio/farmacocinética , Tomografia Computadorizada de Emissão de Fóton Único/métodos
8.
Chem Pharm Bull (Tokyo) ; 67(9): 897-903, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31474726

RESUMO

The word "theranostics," a portmanteau word made by combining "therapeutics" and "diagnostics," refers to a personalized medicine concept. Recently, the word, "radiotheranostics," has also been used in nuclear medicine as a term that refer to the use of radioisotopes for combined imaging and therapy. For radiotheranostics, a diagnostic probe and a corresponding therapeutic probe can be prepared by introducing diagnostic and therapeutic radioisotopes into the same precursor. These diagnostic and therapeutic probes can be designed to show equivalent pharmacokinetics, which is important for radiotheranostics. As imaging can predict the absorbed radiation dose and thus the therapeutic and side effects, radiotheranostics can help achieve the goal of personalized medicine. In this review, I discuss the use of radiolabeled probes targeting bone metastases, sigma-1 receptor, and αVß3 integrin for radiotheranostics.


Assuntos
Neoplasias Ósseas/diagnóstico , Compostos Radiofarmacêuticos/química , Animais , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/radioterapia , Meios de Contraste/química , Meios de Contraste/metabolismo , Humanos , Oligopeptídeos/química , Oligopeptídeos/metabolismo , Oligopeptídeos/uso terapêutico , Compostos Radiofarmacêuticos/farmacocinética , Compostos Radiofarmacêuticos/uso terapêutico , Receptores sigma/química , Receptores sigma/metabolismo , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único , Distribuição Tecidual
9.
Medicine (Baltimore) ; 98(31): e16690, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31374056

RESUMO

This study investigated the clinicopathologic factors associated with 2-[F]fluoro-2-deoxy-D-glucose (F-FDG) uptake of early gastric cancer (EGC) and used them to design a clinical scoring method to predict FDG-avidity of EGC.Two hundred twenty-nine retrospectively enrolled patients underwent preoperative F-FDG positron emission tomography/computed tomography (PET/CT). Histologic information was obtained by gastrectomy (n = 195) or endoscopic mucosal dissection (n = 34). The association between clinicopathologic factors and F-FDG uptake by the primary tumor was determined. The results were used to develop a clinical scoring method.F-FDG uptake was detected in 49 (17.5%) patients. According to univariate analysis, location, gross type, World Health Organization classification, Lauren classification, size, depth of invasion, and lymphatic invasion were significant variables affecting F-FDG uptake (all P < .05). According to multivariate analysis, location (lower 3rd, P = .035), gross type (0-I, 0-IIa, P < .001), size (≥2.5 cm, P = .026), and depth of invasion (submucosa, P = .007) were significantly associated with FDG-avidity. A clinical scoring system, ranged from 0 to 4, was developed by giving one score to 4 independent variables. A cut-off value of 2.5 showed good prediction of FDG-avidity in EGCs, with a sensitivity and specificity of 65.0% and 85.2%, respectively.F-FDG uptake by EGC depends on location, gross type, size, and depth of invasion of the primary tumor. A clinical scoring system based on clinicopathologic variables can predict the FDG-avidity of primary tumors in patients with EGC.


Assuntos
Adenocarcinoma/diagnóstico por imagem , Fluordesoxiglucose F18/farmacocinética , Compostos Radiofarmacêuticos/farmacocinética , Neoplasias Gástricas/diagnóstico por imagem , Adenocarcinoma/patologia , Adulto , Idoso , Detecção Precoce de Câncer/métodos , Feminino , Fluordesoxiglucose F18/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos/administração & dosagem , Estudos Retrospectivos , Neoplasias Gástricas/patologia
10.
PLoS One ; 14(7): e0217384, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31260447

RESUMO

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


Assuntos
Doença de Alzheimer/diagnóstico por imagem , Carbolinas/síntese química , Meios de Contraste/síntese química , Compostos Radiofarmacêuticos/síntese química , Proteínas tau/química , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Animais , Disponibilidade Biológica , Carbolinas/sangue , Carbolinas/farmacocinética , Meios de Contraste/farmacocinética , Avaliação Pré-Clínica de Medicamentos , Expressão Gênica , Haplorrinos , Humanos , Injeções Intravenosas , Macaca , Masculino , Camundongos , Camundongos Endogâmicos ICR , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons/métodos , Radiometria , Compostos Radiofarmacêuticos/sangue , Compostos Radiofarmacêuticos/farmacocinética , Distribuição Tecidual , Proteínas tau/genética
12.
Br J Hosp Med (Lond) ; 80(7): 380-386, 2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31283392

RESUMO

Gliomas are the most common primary brain tumours in children and adults, consisting of a heterogeneous group of neoplastic diseases arise from the supporting cells of the CNS (glial cells). Their histopathological and molecular characteristics vary considerably as do their management and prognosis. Conventional gadolinium-enhanced magnetic resonance imaging (MRI) is considered the primary imaging modality for initial work up and follow up of patients with gliomas, although it has some limitations, especially in differentiating high from low grade tumours and in distinguishing disease recurrence from post-therapy changes. Hybrid positron emission tomography (PET)/MRI is a relatively novel tool that combines MRI sequences with metabolic information from PET, and therefore different PET radiotracers, in a single scan. This article discusses the main advantages and disadvantages of combined PET/MRI compared to other conventional or more widely available imaging tools, such as MRI or combined positron emission tomography-computed tomography. The main uses of PET/MRI and the most commonly used PET radiotracers in providing diagnostic, prognostic and predictive information in patients with glioma are covered.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Glioma/diagnóstico por imagem , Imagem por Ressonância Magnética/métodos , Tomografia por Emissão de Pósitrons/métodos , Humanos , Imagem Multimodal , Estadiamento de Neoplasias , Compostos Radiofarmacêuticos/administração & dosagem , Compostos Radiofarmacêuticos/farmacocinética
13.
Br J Radiol ; 92(1102): 20181051, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31322913

RESUMO

OBJECTIVE: To determine whether the apparent diffusion coefficient (ADC) on 3T MR imaging including diffusion-weighted MR imaging (DWI) correlate with the standardized uptake value (SUV) on 18F-FDG PET/CT in musculoskeletal tumours. METHODS: This retrospective cohort study included 57 patients (36 males, 21 females, mean age 54 years, range 12-90 years) with pathologically confirmed soft tissue (n = 32) and bone (n = 25) tumours who underwent 3T MR imaging including DWI and whole-body 18F-FDG PET/CT before treatment. 14 patients had follow-up MR imaging and 18F-FDG PET/CT after treatment. The minimum (ADCmin) and mean (ADCmean) ADCs of musculoskeletal tumour, ADC of normal skeletal muscle (ADCmus), SUVmax and SUVmean of musculoskeletal tumour were obtained. Correlation between ADCs and SUVs was assessed using Pearson correlation coefficients (r). ADCmin and SUVmax were compared between pretreatment and posttreatment by t-test. RESULTS: There was inverse correlation between SUVmax and the ratio ADCmin/ADCmus (r = - 0.505 to - 0.495, p ≤ 0.001) and between SUVmean and the ratio ADCmean/ADCmus (r = - 0.501 to - 0.493, p = 0.001). After treatment ADC was significantly increased whereas SUV was significantly decreased (p = 0.001). There was significant correlation in percent change between the initial and follow-up values of ADCmin and SUVmax (r = 0.750 to 0.773, p ≤ 0.005). The ADCmin was increased by 163% and SUVmax was decreased by 61% in 11 patients with treatment response. CONCLUSION: ADC at 3T MR DWI and SUV at 18F-FDG PET/CT have an inverse correlation in musculoskeletal tumours. ADVANCES IN KNOWLEDGE: Our study showed that ADC at 3T DWI and SUV at 18F-FDG PET/CT had an inverse correlation in musculoskeletal tumours.


Assuntos
Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/metabolismo , Imagem de Difusão por Ressonância Magnética/métodos , Fluordesoxiglucose F18/metabolismo , Neoplasias Musculares/diagnóstico por imagem , Neoplasias Musculares/metabolismo , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos/farmacocinética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/patologia , Criança , Feminino , Glucose/farmacocinética , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Musculares/patologia , Variações Dependentes do Observador , Estudos Retrospectivos , Fatores de Tempo , Adulto Jovem
14.
Eur Radiol ; 29(12): 6717-6727, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31278574

RESUMO

OBJECTIVES: We recently described metabolic nodal stage (mN) and response (mNR) of cancer of the esophagus and gastro-esophageal junction (GEJ) to neoadjuvant chemotherapy (NAC) using 18F-FDG PET-CT as new markers of disease progression, recurrence, and death. We aimed to validate our findings. METHODS: Our validation cohort comprised all patients consecutive to our discovery cohort, staged before and after NAC using PET-CT from 2014 to 2017. Multivariate binary logistic and Cox regression were performed. RESULTS: Fifty-one of the 200 patients had FDG-avid nodes after NAC (25.5%; i.e., lack of complete mNR), and were more likely to progress during NAC to incurable disease on PET-CT or at surgery: odds ratio 3.84 (1.46-10.1; p = 0.006). In 176 patients undergoing successful resection, patients without complete mNR had a worse prognosis: disease-free survival hazard ratio 2.46 (1.34-4.50); p = 0.004. These associations were independent of primary tumor metabolic, pathological response, and stage. In a hybrid pathological/metabolic nodal stage, avid nodal metastases conferred a worse prognosis than non-avid metastases. Lack of complete mNR predicted recurrence or death at 1 and 2 years: positive predictive values 44.4% (31.7-57.8) and 74.1% (56.6-86.3) respectively. CONCLUSIONS: This study provides temporal validation for mNR as a new and independent predictive and prognostic marker of esophageal and GEJ cancer treated with NAC and surgery, although external validation is required to assess generalizability. mNR may provide surrogate information regarding the phenotype of metastatic cancer clones beyond the mere presence of nodal metastases, and might be used to better inform patients, risk stratify, and personalize management, including adjuvant therapy. KEY POINTS: • We previously described metabolic nodal response (mNR) of esophageal cancer to neoadjuvant chemotherapy using 18 F-FDG PET-CT as a predictor of unresectable disease, early recurrence, and death. • We report the first validation of these findings. In an immediately consecutive cohort, we found consistent proportions of patients with and without mNR, and associations with abandoned resection, early recurrence, and death. • This supports mNR as a new and actionable biomarker in esophageal cancer. Although external validation is required, mNR may provide surrogate information about the chemosensitivity of metastatic subclones, and the means to predict treatment success, guide personalized therapy, and follow-up.


Assuntos
Neoplasias Esofágicas/diagnóstico por imagem , Neoplasias Esofágicas/tratamento farmacológico , Fluordesoxiglucose F18/farmacocinética , Linfonodos/metabolismo , Terapia Neoadjuvante/métodos , Recidiva Local de Neoplasia/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Idoso , Intervalo Livre de Doença , Neoplasias Esofágicas/metabolismo , Junção Esofagogástrica/diagnóstico por imagem , Junção Esofagogástrica/metabolismo , Feminino , Humanos , Linfonodos/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Compostos Radiofarmacêuticos/farmacocinética , Reprodutibilidade dos Testes , Resultado do Tratamento
15.
Int J Radiat Biol ; 95(11): 1547-1551, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31290704

RESUMO

Purpose: This study evaluated if Toxoplasma gondii infection and the drug-associated infection modifies the brain radiopharmaceutical Ethylene Cystine Diethylester Dihydrochloride (99mTc-ECD) biodistribution in mice.Materials and methods: A total of 18 mice were divided into 3 groups. Control group (C) received distilled water and 99mTc-ECD; Infected group (I) received T. gondii strain and 99mTc-ECD; Infected and Treated group (IT), in addition to infection, received association of Pyrimethamine and Sulfadiazine and 99mTc-ECD. The T. gondii strain used in this study was TgCkRrRN3. Forty minutes after administration of the 99mTc-ECD, all animals were euthanized, and blood and brain samples were isolated. The counting of the radioactivity percentage per gram of tissue (%ATI/g) was calculated, and statistical analysis was performed by t-test, with a level of significance of p < .05.Results: There was a significant increase in %ATI/g between groups C and I on brain (0.35 ± 0.02 and 0.45 ± 0.04; p = .041) and on blood (0.80 ± 0.09 and 1.14 ± 0.31; p = .049). A significant decrease in %ATI/g occurred between groups C and IT on blood (0.80 ± 0.09 and 0.54 ± 0.08; p = .001) and on brain (0.35 ± 0.02 and 0.22 ± 0.04; p = .049).Conclusions: Combined therapy of anti-Toxoplasma drugs in infected mice reduced the uptake of 99mTc-ECD, probably due to its binding to plasma proteins.


Assuntos
Encéfalo/parasitologia , Encéfalo/efeitos da radiação , Cisteína/análogos & derivados , Compostos de Organotecnécio/farmacocinética , Compostos Radiofarmacêuticos/farmacocinética , Toxoplasma , Toxoplasmose/tratamento farmacológico , Toxoplasmose/parasitologia , Animais , Antiprotozoários/uso terapêutico , Encéfalo/metabolismo , Cisteína/farmacocinética , Masculino , Camundongos , Pirimetamina/uso terapêutico , Sulfadiazina/uso terapêutico , Distribuição Tecidual
16.
Hell J Nucl Med ; 22(2): 103-110, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31273351

RESUMO

OBJECTIVE: Incorporation of lutetium-177 (177Lu) into suitable molecules that are implicated in cancer pathology represents a promising approach for the diagnosis and treatment of cancer. The goal of the present study was to develop a novel 177Lu labeled radiopharmaceutical agent for both radioimaging and targeted radionuclide therapy. ANIMALS AND METHODS: Given the synthetic versatility of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) ligand as a metal chelator and high demand of sugar molecules such as deoxyglucose (DG) in cancer cells, we carried out the radiosynthesis of a novel radiopharmaceutical agent, namely, 177Lu-DOTA-DG, and utilized it for imaging of cancer and also for the targeted radiation therapy of cancer tissues. RESULTS: In this study, we developed an efficient radiochemical synthesis of 177Lu-DOTA-DG and evaluated its pharmacological properties in vitro/in vivo. Our results showed DOTA-DG can be labeled with 177Lu with excellent radiochemical yield at 90oC in 30min. The resulting 177Lu-DOTA-DG exhibited high degree of stability without significant radiolysis up to 120h in human serum and phosphate buffer. Favorable pharmacokinetics profile was demonstrated by rapid blood clearance in 4T1 murine tumor mice and heterogeneous whole body biodistribution of 177Lu-DOTA-DG. Further, Comet assay experiments indicated that cancer cells treated with 177Lu-DOTA-DG showed significant higher degree of DNA damage compared to cells treated with 177Lu3+ or non-treated cells. CONCLUSION: This study showed that there is a great potential of using 177Lu-DOTA-DG as an imaging and therapeutic agent for cancer diagnosis and treatment. Furthermore, this study provides valuable information for developing novel 177Lu-labeled radiopharmaceuticals.


Assuntos
Desoxiglucose/química , Compostos Heterocíclicos com 1 Anel/química , Lutécio/uso terapêutico , Imagem Molecular/métodos , Radioisótopos/uso terapêutico , Compostos Radiofarmacêuticos/química , Compostos Radiofarmacêuticos/uso terapêutico , Animais , Transporte Biológico , Linhagem Celular Tumoral , Dano ao DNA , Estabilidade de Medicamentos , Marcação por Isótopo , Lutécio/efeitos adversos , Camundongos , Radioquímica , Radioisótopos/efeitos adversos , Compostos Radiofarmacêuticos/efeitos adversos , Compostos Radiofarmacêuticos/farmacocinética , Distribuição Tecidual
17.
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
18.
Clin Nucl Med ; 44(8): 674-675, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31274621

RESUMO

A 30-year-old woman with a recent episode of dyspnea was presented. The lung perfusion scan using Tc-MAA (macro-aggregated albumin) initially revealed an acceptable lung-to-background activity ratio implying a proper radiopharmaceutical preparation and radiolabeling efficiency. Unexpectedly, later during the scan, rapidly increasing concentration of activity was observed in salivary glands, thyroid and stomach. Rapid breakdown of Tc-MAA complexes was considered as a likely explanation for the increase in the circulatory level of the free pertechnetate.


Assuntos
Pulmão/diagnóstico por imagem , Compostos Radiofarmacêuticos/farmacocinética , Agregado de Albumina Marcado com Tecnécio Tc 99m/farmacocinética , Cintilografia de Ventilação/Perfusão , Adulto , Feminino , Humanos , Glândulas Salivares/diagnóstico por imagem , Estômago/diagnóstico por imagem , Glândula Tireoide/diagnóstico por imagem
19.
Medicine (Baltimore) ; 98(27): e16306, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31277170

RESUMO

This study investigated the effect of sex hormones on F-fluorodeoxyglucose (FDG) uptake in normal breast tissue.The retrospective study included 249 premenopausal women (median age, 45 years) who were diagnosed with unilateral breast cancer and underwent FDG positron emission tomography/computed tomography and hormone tests. The volume of interest was within the contralateral normal breast and the standardized uptake values (SUVs) were measured. The correlations of sex hormones (including estrogen, progesterone, testosterone, follicle-stimulating hormone [FSH] and luteinizing hormone [LH]) with the SUVs of the normal breast were analyzed.There was a weak negative correlation between age and breast FDG uptake (P = .012, Spearman coefficient = -.16 for the maximum standardized uptake values [SUVmax]), especially in the luteal phase group (P = .005, Spearman coefficient = -.27 for SUVmax). The SUVs of normal breast tissue were increased when progesterone levels were higher (P = .043, Spearman coefficient = .13 for SUVmax). In the irregular menstrual cycle group, FDG uptake in the breast decreased as FSH (P = .027, Spearman coefficient = -.42 for SUVmax) and LH (P = .048, Spearman coefficient = -.44 for SUVmax) increased.Glucose metabolism of normal breast tissue decreases with age, and progesterone weakly affects breast FDG uptake. Gonadotropins may affect breast FDG uptake in premenopausal women with irregular menstrual cycles.


Assuntos
Mama/metabolismo , Estradiol/sangue , Fluordesoxiglucose F18/farmacocinética , Hormônio Foliculoestimulante/sangue , Hormônio Luteinizante/sangue , Progesterona/sangue , Testosterona/sangue , Adulto , Mama/diagnóstico por imagem , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/metabolismo , Feminino , Humanos , Pessoa de Meia-Idade , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos/farmacocinética , Valores de Referência , Estudos Retrospectivos
20.
PLoS One ; 14(5): e0217515, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31150436

RESUMO

INTRODUCTION: Positron Emission Tomography (PET) imaging with selective 18 kDa translocator protein (TSPO) radiotracers has contributed to our understanding on the role of inflammation in disease development and progression. With an increasing number of rodent models of human disease and expansion of the preclinical PET imaging base worldwide, accurate quantification of longitudinal rodent TSPO PET datasets is necessary. This is particularly relevant as TSPO PET quantification relies on invasive blood sampling due to lack of a suitable tissue reference region. Here we investigate the kinetics and quantification bias of a novel TSPO radiotracer [18F]AB5186 in rats using automatic, manual and image derived input functions. METHODS: [18F]AB5186 was administered intravenously and dynamic PET imaging was acquired over 2 hours. Arterial blood was collected manually to derive a population based input function or using an automatic blood sampler to derive a plasma input function. Manually sampled blood was also used to analyze the [18F]AB5186 radiometabolite profile in plasma and applied to all groups as a population based dataset. Kinetic models were used to estimate distribution volumes (VT) and [18F]AB5186 outcome measure bias was determined. RESULTS: [18F]AB5186 distribution in rats was consistent with TSPO expression and at 2 h post-injection 50% of parent compound was still present in plasma. Population based manual sampling methods and image derived input function (IDIF) underestimated VT by ~50% and 88% compared with automatic blood sampling, respectively. The VT variability was lower when using IDIF versus arterial blood sampling methods and analysis of the Bland-Altman plots showed a good agreement between methods of analysis. CONCLUSION: Quantification of TSPO PET rodent data using image-derived methods, which are more amenable for longitudinal scanning of small animals, yields outcome measures with reduced variability and good agreement, albeit biased, compared with invasive blood sampling methods.


Assuntos
Proteínas de Transporte/antagonistas & inibidores , Imagem Molecular/métodos , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos/farmacocinética , Animais , Radioisótopos de Flúor , Processamento de Imagem Assistida por Computador , Masculino , Modelos Animais , Compostos Radiofarmacêuticos/administração & dosagem , Ratos , Receptores de GABA-A
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