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1.
Radiol Clin North Am ; 59(5): 693-703, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34392913

RESUMO

Precision medicine integrates molecular pathobiology, genetic make-up, and clinical manifestations of disease in order to classify patients into subgroups for the purposes of predicting treatment response and suggesting outcome. By identifying those patients who are most likely to benefit from a given therapy, interventions can be tailored to avoid the expense and toxicity of futile treatment. Ultimately, the goal is to offer the right treatment, to the right patient, at the right time. Lung cancer is a heterogeneous disease both functionally and morphologically. Further, over time, clonal proliferations of cells may evolve, becoming resistant to specific therapies. PET is a sensitive imaging technique with an important role in the precision medicine algorithm of lung cancer patients. It provides anatomo-functional insight during diagnosis, staging, and restaging of the disease. It is a prognostic biomarker in lung cancer patients that characterizes tumoral heterogeneity, helps predict early response to therapy, and may direct the selection of appropriate treatment.


Assuntos
Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Imagem Molecular/tendências , Tomografia por Emissão de Pósitrons/tendências , Medicina de Precisão/tendências , Fluordesoxiglucose F18 , Humanos , Interpretação de Imagem Assistida por Computador , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/tendências , Compostos Radiofarmacêuticos
2.
Eur J Nucl Med Mol Imaging ; 48(9): 2914-2924, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33559712

RESUMO

BACKGROUND: To retrospectively assess liver tumor ablation margins using intraprocedural PET/CT images from FDG PET/CT-guided microwave or cryoablation procedures and to correlate minimum margin measurements with local progression outcomes. METHODS: Fifty-six patients (ages 36 to 85, median 62; 32 females) with 77 FDG-avid liver tumors underwent 60 FDG PET/CT guided, percutaneous microwave, or cryoablation procedures. Single breath-hold PET/CT images were used for intraprocedural assessment of the tumor ablation margin: liver tumors remained visible on PET immediately following ablation; microwave ablation zones were visible using contrast-enhanced CT; cryoablation zones (ice balls) were visible using unenhanced CT. Two readers retrospectively determined ablation margin assessability and measured the minimum ablation margin on intraprocedural PET/CT (n = 77) and postprocedural MRI (n = 56). Local tumor progression was assessed on all available follow-up imaging (1-49 months, mean 15). Local tumor progression was correlated with PET/CT minimum margin measurements using clustered survival models for 61 tumors. RESULTS: Minimum ablation margins were more often assessable using intraprocedural PET/CT (≥ 73/77 tumors, 95%) than postprocedural MRI (≤ 35/56 tumors, 63%). In 61 tumors with PET/CT-assessable margins (excluding tumors with overlapping ablations after PET/CT), there was a 6-fold increased risk of local tumor progression [hazard ratio (HR) 6.05; P = 0.004] for minimum ablation margins < 5 mm. CONCLUSION: Breath-hold PET/CT scans, during PET/CT-guided microwave or cryoablation procedures for FDG-avid liver tumors, enable reliable intraprocedural assessment of the entire tumor ablation margin; a minimum PET/CT ablation margin threshold of 5 mm correlates well with local tumor progression outcomes.


Assuntos
Neoplasias Hepáticas , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Fluordesoxiglucose F18 , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Resultado do Tratamento
3.
Abdom Radiol (NY) ; 46(7): 3437-3447, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33606061

RESUMO

PURPOSE: To evaluate 18F-fluorodeoxyglucose (FDG) perfusion PET during FDG PET/CT-guided liver tumor microwave ablation procedures for assessing the ablation margin and correlating minimum margin measurements with local progression. METHODS: This IRB-approved, HIPAA-compliant study included 20 adult patients (11 M, 9 F; mean age 65) undergoing FDG PET/CT-guided liver microwave ablation to treat 31 FDG-avid tumors. Intraprocedural FDG perfusion PET was performed to assess the ablation margin. Intraprocedural decisions regarding overlapping ablations were recorded. Two readers retrospectively interpreted intraprocedural perfusion PET and postprocedural contrast-enhanced MRI. Assessability of the ablation margin and minimum margin measurements were recorded. Imaging follow-up for local progression ranged from 30 to 574 days (mean 310). Regression modeling of minimum margin measurements was performed. Hazard ratios were calculated to correlate an ablation margin threshold of 5 mm with outcomes. RESULTS: Intraprocedural perfusion PET prompted additional overlapping ablations of two tumors, neither of which progressed. Incomplete ablation or local progression occurred in 8/31 (26%) tumors. With repeat ablation, secondary efficacy was 26 (84%) of 31. Both study readers deemed ablation margins fully assessable more often using perfusion PET than MRI (OR 69.7; CI 6.0, 806.6; p = 0.001). Minimum ablation margins ≥ 5 mm on perfusion PET correlated with a low risk of incomplete ablation/local progression by both study readers (HR 0.08 and 0.02, p < 0.001). CONCLUSION: Intraprocedural FDG perfusion PET consistently enabled complete liver tumor microwave ablation margin assessments, and the perfusion PET minimum ablation margin measurements correlated well with local outcomes. Clinical trial registration clinicaltrials.gov (NCT02018107).


Assuntos
Fluordesoxiglucose F18 , Neoplasias Hepáticas , Adulto , Idoso , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Perfusão , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de Pósitrons , Estudos Retrospectivos
4.
Eur J Nucl Med Mol Imaging ; 48(5): 1618-1625, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33175240

RESUMO

PURPOSE: Poor liver tumor visibility after microwave ablation (MWA) limits direct tumor ablation margin assessments using contrast-enhanced CT or ultrasound (US). Positron emission tomography (PET) or PET/CT may offer improved intraprocedural assessment of liver tumor ablation margins versus current imaging techniques, as 18F-fluorodeoxyglucose (18F-FDG)-avid tumors remain visible on PET immediately following ablation. The purpose of this study was to assess intraprocedural 18F-FDG PET scans before and immediately after PET/CT-guided MWA for visualization and quantification of metabolic liver tumor tissue contraction resulting from MWA. METHODS: This retrospective study, conducted at a large academic medical center after Institutional Review Board approval, included 36 patients (20 men; mean age 63 [range 37-85]) who underwent PET/CT-guided MWA of 42 18F-FDG-avid liver tumors from May 2013 to March 2018. Tumor metabolic diameters (short/long axes) were measured for each tumor on pre- and post-ablation PET images. Tumor metabolic volumes were calculated using tumor diameter measurements and compared with automated volumes using an SUV threshold algorithm. A two-tailed paired t test was used for the analyses. RESULTS: Comparing intraprocedural pre- and post-ablation PET images, mean metabolic tumor short- and long-axis diameters decreased from 21.4 to 14.9 mm [- 29%, p < 0.001, standard deviation (SD) 18%] and from 24.0 to 18.0 mm (- 24%, p < 0.001, SD 16%), respectively. The mean calculated tumor metabolic volume decreased from 10.5 to 4.6 mm3 (- 55%, p < 0.001, SD 26%). The mean automated tumor metabolic volume decreased from 10.6 to 5.8 mm3 (- 45%, p < 0.001, SD 30%). CONCLUSION: Intraprocedural PET images of 18F-FDG-avid liver tumors allow visualization and quantification of MWA-induced metabolic tumor tissue contraction during 18F-FDG PET/CT-guided procedures. The ability to visualize contracted tumor immediately post-MWA may facilitate emerging intraprocedural PET and PET/CT imaging techniques that address a clinical gap in directly assessing the ablation margin.


Assuntos
Fluordesoxiglucose F18 , Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Masculino , Micro-Ondas , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de Pósitrons , Estudos Retrospectivos
5.
Eur J Radiol Open ; 7: 100291, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33304940

RESUMO

Background: A multidisciplinary team approach to the management of esophageal cancer patients leads to better clinical decisions. Purpose: The contribution of CT, endoscopic and laparoscopic ultrasound to clinical staging and treatment selection by multidisciplinary tumor boards (MTB) in patients with esophageal cancer is well documented. However, there is a paucity of data addressing the role that FDG-PET/CT (PET/CT) plays to inform the clinical decision-making process at MTB conferences. The aim of this study was to assess the impact and contribution of PET/CT to clinical management decisions and to the plan of care for esophageal cancer patients at the MTB conferences held at our institution. Materials and methods: This IRB approved study included all the cases discussed in the esophageal MTB meetings over a year period. The information contributed by PET/CT to MTB decision making was grouped into four categories. Category I, no additional information provided for clinical management; category II, equivocal and misguiding information; category III, complementary information to other imaging modalities, and category IV, information that directly changed clinical management. The overall impact on management was assessed retrospectively from prospectively discussed clinical histories, imaging, histopathology, and the official minutes of the MTB conferences. Results: 79 patients (61 males and 18 females; median age, 61 years, range, 33-86) with esophageal cancer (53 adenocarcinomas and 26 squamous cell carcinomas) were included. The contribution of PET/CT-derived information was as follows: category I in 50 patients (63%); category II in 3 patients (4%); category III in 8 patients (10%), and category IV information in 18 patients (23%). Forty-five patients (57%) had systemic disease, and in 5 (11%) of these, metastatic disease was only detected by PET/CT. In addition, PET/CT detected previously unknown recurrence in 4 (9%) of 43 patients. In summary, PET/CT provided clinically useful information to guide management in 26 of 79 esophageal cancer patients (33%) discussed at the MTB. Conclusion: The study showed that PET/CT provided additional information and changed clinical management in 1 out of 3 (33%) esophageal cancer cases discussed at MTB conferences. These results support the inclusion whenever available, of FDG-PET/CT imaging information to augment and improve the patient management decision process in MTB conferences.

6.
Tissue Eng Part C Methods ; 25(1): 49-57, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30560717

RESUMO

IMPACT STATEMENT: The work is notable for describing a highly sensitive, quantitative, and nondestructive method for evaluating the in vitro amount of mineral accompanying different types of osteogenic differentiation of mesenchymal stem cells in a monolayer cell culture. What is so unique and useful about the method is that it has the potential to be used to define the kinetics of the differentiation process, reflected in the mineralization, without destroying the monolayer. Therefore, it remains intact for further experiments.


Assuntos
Medula Óssea , Diferenciação Celular , Células-Tronco Mesenquimais/citologia , Minerais/metabolismo , Osteogênese , Medronato de Tecnécio Tc 99m/metabolismo , Animais , Calcificação Fisiológica , Células Cultivadas , Cabras , Humanos , Células-Tronco Mesenquimais/metabolismo , Compostos Radiofarmacêuticos/metabolismo
7.
Radiology ; 288(1): 138-145, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29613843

RESUMO

Purpose To prospectively determine whether nitrogen 13 (13N) ammonia perfusion positron emission tomography (PET) during fluorine 18 fluorodeoxyglucose (FDG) PET/computed tomography (CT)-guided liver tumor ablation can be used to intraprocedurally assess ablation margins. Materials and Methods Eight patients (five women and three men; age range, 36-74 years; mean age, 57 years) were enrolled in this pilot study and underwent FDG PET/CT-guided microwave ablation of 11 FDG-avid liver metastases (mean diameter, 22 mm; range, 11-34 mm). All procedures were performed between March 2014 and December 2016. Complete ablation margin visibility and minimum ablation margin thickness were assessed by using intraprocedural 13N-ammonia perfusion PET compared with 24-hour postprocedural MR imaging by two independent blinded radiologists. Local tumor progression for each ablated tumor was assessed at follow-up imaging for 3-38 months (median, 17.6 months). Descriptive analysis was performed. Results Eleven of 11 (100%) ablation margins were fully assessable by using intraprocedural perfusion PET by both readers; six of eleven (55%) margins were fully assessable by both readers at postprocedural 24-hour MR imaging. By using perfusion PET, one tumor that had been judged by both readers to have a minimum margin of 0 mm progressed locally. No tumors judged to have a minimum margin greater than 0 mm at perfusion PET progressed locally. Conclusion 13N-ammonia perfusion PET during FDG PET/CT-guided liver tumor ablations can potentially be used to intraprocedurally assess the entire ablation margin, including the minimum margin. © RSNA, 2018.


Assuntos
Técnicas de Ablação/métodos , Fluordesoxiglucose F18 , Neoplasias Hepáticas/diagnóstico por imagem , Radioisótopos de Nitrogênio , Tomografia por Emissão de Pósitrons/métodos , Radiografia Intervencionista/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Fígado/diagnóstico por imagem , Fígado/cirurgia , Neoplasias Hepáticas/cirurgia , Masculino , Micro-Ondas , Pessoa de Meia-Idade , Projetos Piloto , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Estudos Prospectivos , Compostos Radiofarmacêuticos
8.
Ann Nucl Med ; 32(3): 165-174, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29332233

RESUMO

OBJECTIVE: The aim of this prospective pilot study was to investigate the potential of serial FLT-PET/CT compared to FDG-PET/CT to provide an early indication of esophageal cancer response to concurrent neoadjuvant chemoradiation therapy. METHODS: Five patients with biopsy-proven esophageal adenocarcinomas underwent neoadjuvant chemoradiation (Tx) prior to minimally invasive esophagectomy. The presence of residual tumor was classified histologically using the Mandard et al. criteria, categorizing patients as pathologic responders and non-responders. Participants underwent PET/CT imaging 1 h after intravenous administration of FDG and of FLT on two separate days within 48 h of each other. Each patient underwent a total of 3 scan "pairs": (1) pre-treatment, (2) during treatment, and (3) post-treatment. Image-based response to therapy was measured in terms of changes in SUVmax (ΔSUV) between pre- and post-therapeutic FLT- and FDG-PET scans. The PET imaging findings were correlated with the pathology results after surgery. RESULTS: All tumors were FDG and FLT avid at baseline. Lesion FLT uptake was lower than with FDG. Neoadjuvant chemoradiation resulted in a reduction of tumor uptake of both radiotracers in pathological responders (n = 3) and non-responders (n = 2). While the difference in the reduction in mean tumor FLT uptake during Tx between responders (ΔSUV = - 55%) and non-responders (ΔSUV = - 29%) was significant (P = 0.007), for FDG it was not, [responders had a mean ΔSUV = - 39 vs. - 31% for non-responders (P = 0.74)]. The difference in the reduction in tumor FLT uptake at the end of treatment between responders (ΔSUV = - 62%) and non-responders (ΔSUV = - 57%) was not significant (P = 0.54), while for FDG there was a trend toward significance [ΔSUV of responders = - 74 vs. - 52% in non-responders (P = 0.06)]. CONCLUSION: The results of this prospective pilot study suggest that early changes in tumor FLT uptake may be better than FDG in predicting response of esophageal adenocarcinomas to neoadjuvant chemoradiation. These preliminary results support the need to corroborate the value of FLT-PET/CT in a larger cohort.


Assuntos
Adenocarcinoma/diagnóstico por imagem , Neoplasias Esofágicas/diagnóstico por imagem , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Compostos Radiofarmacêuticos , Adenocarcinoma/metabolismo , Adenocarcinoma/terapia , Idoso , Quimiorradioterapia Adjuvante , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/terapia , Esofagectomia , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos , Projetos Piloto , Estudos Prospectivos
9.
Nucl Med Mol Imaging ; 51(1): 3-10, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28250852

RESUMO

The increased understanding of the molecular pathology of different malignancies, especially lung cancer, has directed investigational efforts to center on the identification of different molecular targets and on the development of targeted therapies against these targets. A good representative is the epidermal growth factor receptor (EGFR); a major driver of non-small cell lung cancer tumorigenesis. Today, tumor growth inhibition is possible after treating lung tumors expressing somatic mutations of the EGFR gene with tyrosine kinase inhibitors (TKI). This opened the doors to biomarker-directed precision or personalized treatments for lung cancer patients. The success of these targeted anticancer therapies depends in part on being able to identify biomarkers and their patho-molecular make-up in order to select patients that could respond to specific therapeutic agents. While the identification of reliable biomarkers is crucial to predict response to treatment before it begins, it is also essential to be able to monitor treatment early during therapy to avoid the toxicity and morbidity of futile treatment in non-responding patients. In this context, we share our perspective on the role of PET imaging-based phenotyping in the personalized care of lung cancer patients to non-invasively direct and monitor the treatment efficacy of TKIs in clinical practice.

10.
PET Clin ; 12(1): 53-62, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27863566

RESUMO

Precision medicine allows tailoring of preventive or therapeutic interventions to avoid the expense and toxicity of futile treatment given to those who will not respond. Lung cancer is a heterogeneous disease functionally and morphologically. PET is a sensitive molecular imaging technique with a major role in the precision medicine algorithm of patients with lung cancer. It contributes to the precision medicine of lung neoplasia by interrogating tumor heterogeneity throughout the body. It provides anatomofunctional insight during diagnosis, staging, and restaging of the disease. It is a biomarker of tumoral heterogeneity that helps direct selection of the most appropriate treatment, the prediction of early response to cytotoxic and cytostatic therapies, and is a prognostic biomarker in patients with lung cancer.


Assuntos
Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/terapia , Imagem Molecular , Tomografia por Emissão de Pósitrons/métodos , Medicina de Precisão , Biomarcadores Tumorais , Humanos , Neoplasias Pulmonares/patologia , Terapia de Alvo Molecular , Valor Preditivo dos Testes , Prognóstico , Compostos Radiofarmacêuticos
11.
Clin Nucl Med ; 41(4): 274-7, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26825201

RESUMO

PURPOSE: Increased 67Ga uptake in the mediastinal/hilar lymph nodes ("lambda") and in the lacrimal/parotid/submandibular glands ("panda") often coexists in patients with sarcoidosis (Sarc-Pts). However, we observed that increased lacrimal/salivary uptake is uncommon on 18F-FDG PET/CT (FDG-panda) in many Sarc-Pts who showed increased mediastinal/hilar uptake (FDG-lambda). We evaluated parotid and lacrimal FDG activity in Sarc-Pts who showed FDG-lambda in comparison with a control patient group and attempted to find underlying mechanisms to explain the discrepancy between FDG and Ga uptake in these organs. METHODS: Parotid FDG activity (FDG-P) was assessed visually using a 0- to 3-point scale (0 being = or minimally > background, and 3 > liver) and quantitatively using SUVmean in 52 confirmed Sarc-Pts with FDG-lambda (lambda group) as well as in 52 non-Sarc-Pts (control group). Lacrimal FDG activity (FDG-L) was assessed visually (0 being = or minimally > subcutaneous tissue, and 1 clearly > subcutaneous tissue). RESULTS: There was no significant difference in the parotid SUVmean between lambda (1.88 ± 0.65) and control (1.76 ± 0.62) groups (P = 0.333). Also, there was no difference in visually graded FDG-P between the 2 groups (P = 0.257). None of the patients in all groups showed apparently abnormal (grade 1) FDG-L. CONCLUSIONS: Increased FDG-L/FDG-P is rare in Sarc-Pts demonstrating FDG-lambda, which is strikingly different from the clinical experience as well as the reported data on Ga scintigraphy. Discrepancy in various cytokine levels between lacrimal samples and intrathoracic lesions in Sarc-Pts reported in the literature appears to correlate well with variable Ga and FDG uptake in the lacrimal gland and intrathoracic lesions.


Assuntos
Fluordesoxiglucose F18 , Aparelho Lacrimal/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Glândulas Salivares/diagnóstico por imagem , Sarcoidose/diagnóstico por imagem , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Imagem Multimodal , Glândula Parótida/diagnóstico por imagem , Tomografia Computadorizada por Raios X
12.
Clin Nucl Med ; 41(3): 253-4, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26562578

RESUMO

It is often challenging to assess renal activity on FDG-PET/CT due to intense physiological activity in the collecting system, thus any unusual intrarenal activity should be evaluated carefully. While increased bone tracer uptake in the irradiated region of the kidneys has been reported in the literature, altered biodistribution of FDG in irradiated renal tissue is not well described. We report a case of FDG PET/CT showing increased FDG activity in small portions of the kidneys that were previously irradiated.


Assuntos
Nefrite/diagnóstico por imagem , Lesões por Radiação/diagnóstico por imagem , Fluordesoxiglucose F18 , Humanos , Imagem Multimodal , Nefrite/etiologia , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Tomografia Computadorizada por Raios X
13.
PLoS One ; 10(8): e0134825, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26284517

RESUMO

Malignant pleural mesothelioma is a highly chemoresistant solid tumor. We have studied this apoptotic resistance using in vitro and ex vivo three-dimensional models, which acquire a high level of chemoresistance that can be reduced by PI3K/mTOR inhibitors. Here, we investigate the activity of GDC-0980, a novel dual PI3K/mTOR inhibitor, which has been proposed to be effective in mesothelioma. In this work, we aimed to identify mechanisms and markers of efficacy for GDC-0980 by utilizing 3D models of mesothelioma, both in vitro multicellular spheroids and ex vivo tumor fragment spheroids grown from patient tumor samples. We found that a subset of mesothelioma spheroids is sensitive to GDC-0980 alone and to its combination with chemotherapy. Unexpectedly, this sensitivity did not correlate with the activation of the Akt/mTOR pathway. Instead, sensitivity to GDC-0980 correlated with the presence of constitutive ATG13 puncta, a feature of autophagy, a cellular program that supports cells under stress. In tumor fragment spheroids grown from 21 tumors, we also found a subset (n = 11) that was sensitive to GDC-0980, a sensitivity that also correlated with the presence of ATG13 puncta. Interference with autophagy by siRNA of ATG7, an essential autophagic protein, increased the response to chemotherapy, but only in the sensitive multicellular spheroids. In the spheroids resistant to GDC-0980, autophagy appeared to play no role. In summary, we show that GDC-0980 is effective in mesothelioma 3D models that display ATG13 puncta, and that blockade of autophagy increases their response to chemotherapy. For the first time, we show a role for autophagy in the response to chemotherapy of 3D models of mesothelioma and propose ATG13 as a potential biomarker of the therapeutic responsiveness of mesothelioma.


Assuntos
Autofagia/efeitos dos fármacos , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Mesotelioma/tratamento farmacológico , Pirimidinas/farmacologia , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteína 7 Relacionada à Autofagia , Proteínas Relacionadas à Autofagia , Biomarcadores/metabolismo , Linhagem Celular Tumoral , Humanos , Neoplasias Pulmonares/metabolismo , Mesotelioma/metabolismo , Mesotelioma Maligno , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Esferoides Celulares/efeitos dos fármacos , Esferoides Celulares/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Enzimas Ativadoras de Ubiquitina/metabolismo
14.
Am J Nucl Med Mol Imaging ; 5(1): 72-82, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25625029

RESUMO

To evaluate (18)F-labeled-fluorodeoxyglucose ((18)F-FDG-) and (18)F-labeled-sodium fluoride ((18)F-NaF-) positron emission tomography/computed tomography (PET/CT) as biomarkers in metastatic castrate-resistant prostate cancer (mCRPC). Nine men (53-75 years) in a phase 1 trial of abiraterone and cabozantinib had (18)F-FDG-PET/CT, (18)F-NaF-PET/CT and standard imaging ((99m)Tc-labeled-methylene-diphosphonate ((99m)Tc-MDP) bone scan and abdominal/pelvic CT) at baseline and after 8 weeks of therapy. Baseline disease was classified as widespread (18)F-FDG-avid, oligometastatic (18)F-FDG-avid (1 site), or non-(18)F-FDG-avid. Metabolic response was classified using European Organisation for Research and Treatment of Cancer (EORTC) criteria. Treatment response using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, Prostate Cancer Working Group 2 (PCWG2) guidelines and days on trial (DOT) were recorded. All men were followed for 1 year or until progression. Four men had (18)F-FDG-avid disease: two with widespread (DOT 53 and 76) and two with oligometastatic disease (DOT 231 and still on trial after 742+ days). Five men had non-(18)F-FDG-avid disease; three remained stable or improved (2 still on trial while one discontinued for non-oncologic reasons; DOT 225-563+), and 2 progressed (DOT 285 and 532). Despite the small sample size, Kaplan-Meier analysis showed a significant difference in progression free survival (PFS) between men with widespread (18)F-FDG-avid, oligometastatic (18)F-FDG-avid and non-(18)F-FDG-avid disease (p < 0.01). All men had (18)F-NaF-avid disease. Neither (18)F-NaF-avid disease extent nor intensity was predictive of treatment response. (18)F-FDG-PET/CT may be superior to (18)F-NaF-PET/CT and standard imaging in men with mCRPC on abiraterone and cabozantinib. (18)F-FDG-PET/CT may have potential to stratify men into 3 groups (widespread vs. oligometastatic (18)F-FDG-avid vs. non-(18)F-FDG-avid mCRPC) to tailor therapy. Further evaluation is warranted.

15.
Ann Clin Transl Neurol ; 1(10): 788-98, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25493270

RESUMO

OBJECTIVE: Cancer patients may experience neurologic adverse effects, such as alterations in neurocognitive function, as a consequence of chemotherapy. The mechanisms underlying such neurotoxic syndromes remain poorly understood. We here describe the temporal and regional effects of systemically administered platinum-based chemotherapy on glucose metabolism in the brain of cancer patients. METHODS: Using sequential FDG-PET/CT imaging prior to and after administration of chemotherapy, we retrospectively characterized the effects of intravenously administered chemotherapy on brain glucose metabolism in a total of 24 brain regions in a homogenous cohort of 10 patients with newly diagnosed non-small-cell lung cancer. RESULTS: Significant alterations of glucose metabolism were found in response to chemotherapy in all gray matter structures, including cortical structures, deep nuclei, hippocampi, and cerebellum. Metabolic changes were also notable in frontotemporal white matter (WM) network systems, including the corpus callosum, subcortical, and periventricular WM tracts. INTERPRETATION: Our data demonstrate a decrease in glucose metabolism in both gray and white matter structures associated with chemotherapy. Among the affected regions are those relevant to the maintenance of brain plasticity and global neurologic function. This study potentially offers novel insights into the spatial and temporal effects of systemic chemotherapy on brain metabolism in cancer patients.

16.
PET Clin ; 9(2): 147-68, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25030279

RESUMO

This article describes the normal patterns of thoracic (18)F-fluorodeoxyglucose (FDG) biodistribution, and expands on the role of FDG-PET/computed tomography (CT) for the evaluation of patients suffering from a spectrum of benign pathologic conditions that affect the chest. The discussion addresses the applications of FDG-PET/CT imaging in a wide variety of chest-related disorders. Familiarity with the normal thoracic biodistribution of FDG, coupled with knowledge of the potential nonmalignant causes of increased FDG uptake in the chest, is essential to minimize the incidence of incorrect interpretation of FDG-PET images in daily clinical practice.


Assuntos
Fluordesoxiglucose F18 , Imagem Multimodal/métodos , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos , Doenças Torácicas/diagnóstico por imagem , Tórax/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Amiloidose/diagnóstico por imagem , Fluordesoxiglucose F18/farmacocinética , Gastroenteropatias/diagnóstico por imagem , Gastroenteropatias/metabolismo , Cardiopatias/diagnóstico por imagem , Humanos , Infecções/diagnóstico por imagem , Pneumopatias/diagnóstico por imagem , Doenças do Mediastino/diagnóstico por imagem , Miocárdio/metabolismo , Doenças Pleurais/diagnóstico por imagem , Doenças Pleurais/metabolismo , Compostos Radiofarmacêuticos/farmacocinética , Sarcoidose/diagnóstico por imagem , Doenças da Coluna Vertebral/diagnóstico por imagem , Doenças Torácicas/metabolismo , Traumatismos Torácicos/diagnóstico por imagem , Vértebras Torácicas/diagnóstico por imagem , Distribuição Tecidual
17.
Acad Radiol ; 21(6): 733-42, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24809315

RESUMO

RATIONALE AND OBJECTIVES: To determine the intraobserver and interobserver variabilities of thymic measurements on computed tomography (CT) in patients with pathologic diagnosis of thymic hyperplasia or normal thymus. MATERIALS AND METHODS: Thirty-three patients with pathologic diagnosis of thymic hyperplasia (n = 25) or normal thymus (n = 8) who had identifiable thymus gland on CT were retrospectively studied. Two radiologists independently measured thymic size and CT attenuation. Concordance correlation coefficients (CCCs) and Bland-Altman plots were used to assess intraobserver and interobserver agreements. RESULTS: The intraobserver and interobserver agreements of thymic diameters and the lobe length were moderate, with CCCs ranging from 0.73 to 0.89 and from 0.72 to 0.81, respectively. Higher agreement was noted among patients whose measurements were performed on the same CT image in two independent measurements, with intraobserver CCC ≥ 0.95 for diameters and length. After providing readers with an instruction for consistent selection of CT image for measurements, the intraobserver and interobserver agreements improved, resulting in CCCs ranging from 0.81 to 0.92 and from 0.77 to 0.85 for diameters and length, respectively. Thymic lobe thickness had the least agreement. CT attenuation measurements were highly reproducible, with CCCs ranging from 0.88 to 0.97. In patients with thymic CT attenuation >30 HU (Hounsfield unit), the attenuation measurements were more reproducible with narrower 95% limits of agreement. CONCLUSIONS: Thymic size measurements had moderate-to-high intraobserver and interobserver agreements, when the instruction for consistent selection of images was provided to the readers. CT attenuation was highly reproducible, with higher reproducibility for thymic glands with >30 HU. Awareness of thymic measurement variability is necessary when interpreting measured values of normal thymus and thymic pathology on CT.


Assuntos
Timo/diagnóstico por imagem , Hiperplasia do Timo/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Reprodutibilidade dos Testes , Estudos Retrospectivos , Timo/anatomia & histologia , Adulto Jovem
18.
AJR Am J Roentgenol ; 202(3): 471-8, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24555583

RESUMO

OBJECTIVE: The purpose of this article is to investigate the imaging characteristics of pathologically proven thymic hyperplasia and to identify features that can differentiate true hyperplasia from lymphoid hyperplasia. MATERIALS AND METHODS: Thirty-one patients (nine men and 22 women; age range, 20-68 years) with pathologically confirmed thymic hyperplasia (18 true and 13 lymphoid) who underwent preoperative CT (n=27), PET/CT (n=5), or MRI (n=6) were studied. The length and thickness of each thymic lobe and the transverse and anterior-posterior diameters and attenuation of the thymus were measured on CT. Thymic morphologic features and heterogeneity on CT and chemical shift on MRI were evaluated. Maximum standardized uptake values were measured on PET. Imaging features between true and lymphoid hyperplasia were compared. RESULTS: No significant differences were observed between true and lymphoid hyperplasia in terms of thymic length, thickness, diameters, morphologic features, and other qualitative features (p>0.16). The length, thickness, and diameters of thymic hyperplasia were significantly larger than the mean values of normal glands in the corresponding age group (p<0.001). CT attenuation of lymphoid hyperplasia was significantly higher than that of true hyperplasia among 15 patients with contrast-enhanced CT (median, 47.9 vs 31.4 HU; Wilcoxon p=0.03). The receiver operating characteristic analysis yielded greater than 41.2 HU as the optimal threshold for differentiating lymphoid hyperplasia from true hyperplasia, with 83% sensitivity and 89% specificity. A decrease of signal intensity on opposed-phase images was present in all four cases with in- and opposed-phase imaging. The mean maximum standardized uptake value was 2.66. CONCLUSION: CT attenuation of the thymus was significantly higher in lymphoid hyperplasia than in true hyperplasia, with an optimal threshold of greater than 41.2 HU in this cohort of patients with pathologically confirmed thymic hyperplasia.


Assuntos
Imagem Multimodal/métodos , Tomografia por Emissão de Pósitrons/métodos , Pseudolinfoma/diagnóstico , Hiperplasia do Timo/diagnóstico , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
19.
Med Phys ; 40(8): 082501, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23927346

RESUMO

PURPOSE: A well-established approach for diagnostic imaging of osteomyelitis (OM), a bone infection, is simultaneous SPECT-CT of 99mTc sulfur colloid (SC) and 111In white blood cells (WBC). This method provides essentially perfect spatial registration of the tracers within anatomic sites of interest. Currently, diagnosis is based purely on a visual assessment-where relative discordance between 99mTc and 111In uptake in bone, i.e., high 111In and low 99mTc, suggests OM. To achieve more quantitative images, noise, scatter, and crosstalk between radionuclides must be addressed through reconstruction. Here the authors compare their Monte Carlo-based joint OSEM (MC-JOSEM) algorithm, which reconstructs both radionuclides simultaneously, to a more conventional triple-energy window-based reconstruction (TEW-OSEM), and to iterative reconstruction with no compensation for scatter (NC-OSEM). METHODS: The authors created numerical phantoms of the foot and torso. Multiple bone-infection sites were modeled using high-count Monte Carlo simulation. Counts per voxel were then scaled to values appropriate for 111In WBC and 99mTc SC imaging. Ten independent noisy projection image sets were generated by drawing random Poisson deviates from these very low-noise images. Data were reconstructed using the two iterative scatter-compensation methods, TEW-OSEM and MC-JOSEM, as well as the uncorrected method (NC-OSEM). Mean counts in volumes of interest (VOIs) were used to evaluate the bias and precision of each method. Data were also acquired using a phantom, approximately the size of an adult ankle, consisting of regions representing infected and normal bone marrow, within a bone-like attenuator and surrounding soft tissue; each compartment contained a mixture of 111In and 99mTc. Low-noise data were acquired during multiple short scans over 29 h on a Siemens Symbia T6 SPECT-CT with medium-energy collimators. Pure 99mTc and 111In projection datasets were derived by fitting the acquired projections to the sum of 99mTc and 111In contributions, using the known half-lives. Uncontaminated data were scaled and recombined into six datasets with different activity ratios; ten Poisson noise realizations were then generated for each ratio. VOIs in each of the compartments were used to evaluate the bias and precision of each method with respect to reconstructions of uncontaminated datasets. In addition to the simulated and acquired phantom images, the authors reconstructed patient images with MC-JOSEM and TEW-OSEM. Patient reconstructions were assessed qualitatively for lesion contrast, spatial definition, and scatter. RESULTS: For all simulated and acquired infection phantoms, the root-mean squared-error of measured 99mTc activity was significantly improved with MC-JOSEM and TEW-OSEM in comparison to NC-OSEM reconstructions. While MC-JOSEM trended toward outperforming TEW-OSEM, the improvement was only found to be significant (p<0.001) for the acquired bone phantom in which a wide range of 111In∕99mTc concentration ratios were tested. In all cases, scatter correction did not significantly improve 111In quantitation. CONCLUSIONS: Compensation for scatter and crosstalk is useful for improving quality, bias, and precision of 99mTc activity estimates in simultaneous dual-radionuclide imaging of OM. The use of the more rigorous MC-based estimates provided marginal improvements over TEW. While the phantom results were encouraging, more subjects are needed to evaluate the usefulness of quantitative 111In∕99mTc SPECT-CT in the clinic.


Assuntos
Radioisótopos de Índio , Imagem Multimodal/métodos , Osteomielite/diagnóstico por imagem , Tecnécio , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Tomografia Computadorizada por Raios X/métodos , Adulto , Pé/diagnóstico por imagem , Humanos , Imagens de Fantasmas , Fatores de Tempo , Tronco/diagnóstico por imagem
20.
Artigo em Inglês | MEDLINE | ID: mdl-23484183

RESUMO

The aim of this study was to evaluate the effects of an osteogenic medium supplemented with platelet-derived growth factor (PDGF) BB and osteogenic protein (OP) 1 on the proliferation and differentiation of mesenchymal stem cells (MSCs) in an anorganic bovine cancellous bone scaffold. At day 7, there was a statistically significant increase in the number of cells in the scaffolds in the group treated with the medium supplemented with both PDGF-BB and OP-1 when compared with the control groups. The highest alkaline phosphate levels, at 14 and 21 days, were recorded for the samples in medium supplemented with OP-1 alone reflecting osteogenic differentiation. The results commend OP-1, as well as PDGF-BB, for incorporation into porous mineral scaffolds for vertical ridge augmentation.


Assuntos
Indutores da Angiogênese/farmacologia , Matriz Óssea , Proteína Morfogenética Óssea 7/farmacologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-sis/farmacologia , Tecidos Suporte , Fosfatase Alcalina/análise , Animais , Becaplermina , Matriz Óssea/química , Bovinos , Adesão Celular/efeitos dos fármacos , Contagem de Células , Técnicas de Cultura de Células , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Meios de Cultura , DNA/análise , Feminino , Cabras , Microscopia Eletrônica de Varredura , Minerais/química , Osteogênese/efeitos dos fármacos , Porosidade , Compostos Radiofarmacêuticos , Proteínas Recombinantes , Medronato de Tecnécio Tc 99m , Fatores de Tempo , Engenharia Tecidual , Tecidos Suporte/química
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