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1.
J Clin Oncol ; 39(2): 116-125, 2021 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-33151787

RESUMO

PURPOSE: 18F-Fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) is currently the standard technique to define minimal residual disease (MRD) status outside the bone marrow (BM) in patients with multiple myeloma (MM). This study aimed to define criteria for PET complete metabolic response after therapy, jointly analyzing a subgroup of newly diagnosed transplantation-eligible patients with MM enrolled in two independent European randomized phase III trials (IFM/DFCI2009 and EMN02/HO95). PATIENTS AND METHODS: Two hundred twenty-eight patients were observed for a median of 62.9 months. By study design, PET/CT scans were performed at baseline and before starting maintenance (premaintenance [PM]). The five-point Deauville scale (DS) was applied to describe BM (BM score [BMS]) and focal lesion (FL; FL score [FS]) uptake and tested a posteriori in uni- and multivariable analyses for their impact on clinical outcomes. RESULTS: At baseline, 78% of patients had FLs (11% extramedullary), 80% with an FS ≥ 4. All patients had BM diffuse uptake (35.5% with BMS ≥ 4). At PM, 31% of patients had visually detectable FLs (2% extramedullary), 24% and 67.7% of them with an FS of 3 and ≥ 4, respectively. At PM, 98% of patients retained residual BM diffuse uptake, which was significantly lower than at baseline (mainly between BMS 2 and 3, BMS was ≥ 4 in only 8.7% of patients). By both uni- and multivariable analysis, FS and BMS < 4 were associated with prolonged progression-free survival (PFS) and overall survival (OS) at PM (OS: hazard ratio [HR], 0.6 and 0.47, respectively; PFS: HR, 0.36 and 0.24, respectively). CONCLUSION: FL and BM FDG uptake lower than the liver background after therapy was an independent predictor for improved PFS and OS and can be proposed as the standardized criterion of PET complete metabolic response, confirming the value of the DS for patients with MM.

2.
EJNMMI Phys ; 7(1): 63, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33044651

RESUMO

BACKGROUND: Internal dosimetry evaluation consists of a multi-step process ranging from imaging acquisition to absorbed dose calculations. Assessment of uncertainty is complicated and, for that reason, it is commonly ignored in clinical routine. However, it is essential for adequate interpretation of the results. Recently, the EANM published a practical guidance on uncertainty analysis for molecular radiotherapy based on the application of the law of propagation of uncertainty. In this study, we investigated the overall uncertainty on a sample of a patient following the EANM guidelines. The aim of this study was to provide an indication of the typical uncertainties that may be expected from performing dosimetry, to determine parameters that have the greatest effect on the accuracy of calculations and to consider the potential improvements that could be made if these effects were reduced. RESULTS: Absorbed doses and the relative uncertainties were calculated for a sample of 49 patients and a total of 154 tumours. A wide range of relative absorbed dose uncertainty values was observed (14-102%). Uncertainties associated with each quantity along the absorbed dose calculation chain (i.e. volume, recovery coefficient, calibration factor, activity, time-activity curve fitting, time-integrated activity and absorbed dose) were estimated. An equation was derived to describe the relationship between the uncertainty in the absorbed dose and the volume. The largest source of error was the VOI delineation. By postulating different values of FWHM, the impact of the imaging system spatial resolution on the uncertainties was investigated. DISCUSSION: To the best of our knowledge, this is the first analysis of uncertainty in molecular radiotherapy based on a cohort of clinical cases. Wide inter-lesion variability of absorbed dose uncertainty was observed. Hence, a proper assessment of the uncertainties associated with the calculations should be considered as a basic scientific standard. A model for a quick estimate of uncertainty without implementing the entire error propagation schema, which may be useful in clinical practice, was presented. Ameliorating spatial resolution may be in future the key factor for accurate absorbed dose assessment.

3.
Expert Opin Pharmacother ; 21(18): 2317-2324, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32990061

RESUMO

BACKGROUND: Somatostatin receptor ligands including octreotide LAR are first-line therapy in locally advanced or metastatic NETs that are nonresectable and well differentiated and are recommended as first-line therapy in functioning and in G1/low G2 nonfunctioning NETs. However, several questions remain that are not adequately addressed in current guidelines regarding its use in clinical scenarios in which the tumor progresses. These include use of nonconventional doses or schedules of octreotide LAR in tumors with hormonal symptoms or showing clinical-radiological progression, administration in combination with everolimus, peptide receptor radionuclide therapy, and chemotherapy, following first-line treatment with octreotide LAR. METHODS: An expert panel was gathered to obtain consensus using Delphi methodology on a series of statements regarding further administration of octreotide LAR after its use in first-line therapy in these settings in patients who experience disease progression. RESULTS: Consensus was reached for 8 of the 10 statements proposed in the above clinical scenarios; consensus was not achieved for two statements. CONCLUSIONS: The present statements aim to fill current gaps in treatment guidelines by providing recommendations based on expert consensus in clinical settings in which patients progress following first-line therapy with octreotide LAR.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Everolimo/uso terapêutico , Tumores Neuroendócrinos/tratamento farmacológico , Octreotida/uso terapêutico , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Hormonais/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Preparações de Ação Retardada , Everolimo/administração & dosagem , Everolimo/efeitos adversos , Feminino , Humanos , Itália , Masculino , Tumores Neuroendócrinos/patologia , Octreotida/administração & dosagem , Octreotida/efeitos adversos , Guias de Prática Clínica como Assunto , Inquéritos e Questionários
4.
PLoS One ; 15(8): e0236466, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32764764

RESUMO

AIM: The present work concerns the comparison of the performances of three systems for dosimetry in RPT that use different techniques for absorbed dose calculation (organ-level dosimetry, voxel-level dose kernel convolution and Monte Carlo simulations). The aim was to assess the importance of the choice of the most adequate calculation modality, providing recommendations about the choice of the computation tool. METHODS: The performances were evaluated both on phantoms and patients in a multi-level approach. Different phantoms filled with a 177Lu-radioactive solution were used: a homogeneous cylindrical phantom, a phantom with organ-shaped inserts and two cylindrical phantoms with inserts different for shape and volume. A total of 70 patients with NETs treated by PRRT with 177Lu-DOTATOC were retrospectively analysed. RESULTS: The comparisons were performed mainly between the mean values of the absorbed dose in the regions of interest. A general better agreement was obtained between Dose kernel convolution and Monte Carlo simulations results rather than between either of these two and organ-level dosimetry, both for phantoms and patients. Phantoms measurements also showed the discrepancies mainly depend on the geometry of the inserts (e.g. shape and volume). For patients, differences were more pronounced than phantoms and higher inter/intra patient variability was observed. CONCLUSION: This study suggests that voxel-level techniques for dosimetry calculation are potentially more accurate and personalized than organ-level methods. In particular, a voxel-convolution method provides good results in a short time of calculation, while Monte Carlo based computation should be conducted with very fast calculation systems for a possible use in clinics, despite its intrinsic higher accuracy. Attention to the calculation modality is recommended in case of clinical regions of interest with irregular shape and far from spherical geometry, in which Monte Carlo seems to be more accurate than voxel-convolution methods.


Assuntos
Lutécio/química , Imagens de Fantasmas/estatística & dados numéricos , Radioisótopos/química , Radiometria/estatística & dados numéricos , Receptores de Peptídeos/isolamento & purificação , Algoritmos , Humanos , Método de Monte Carlo , Doses de Radiação , Receptores de Peptídeos/química , Estudos Retrospectivos
5.
Curr Radiopharm ; 13(3): 204-217, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32186275

RESUMO

INTRODUCTION: In patients suitable for radical chemoradiotherapy for lung cancer, 18F-FDGPET/ CT is a proposed management to improve the accuracy of high dose radiotherapy. However, there is a high rate of locoregional failure in patients with locally advanced non-small cell lung cancer (NSCLC), probably due to the fact that standard dosing may not be effective in all patients. The aim of the present review was to address some criticisms associated with the radiotherapy image-guided in NSCLC. MATERIALS AND METHODS: A systematic literature search was conducted. Only published articles that met the following criteria were included: articles, only original papers, radiopharmaceutical ([18F]FDG and any tracer other than [18F]FDG), target, only specific for lung cancer radiotherapy planning, and experimental design (eventually "in vitro" studies were excluded). Peer-reviewed indexed journals, regardless of publication status (published, ahead of print, in press, etc.) were included. Reviews, case reports, abstracts, editorials, poster presentations, and publications in languages other than English were excluded. The decision to include or exclude an article was made by consensus and any disagreement was resolved through discussion. RESULTS: Hundred eligible full-text articles were assessed. Diverse information is now available in the literature about the role of FDG and new alternative radiopharmaceuticals for the planning of radiotherapy in NSCLC. In particular, the role of alternative technologies for the segmentation of FDG uptake is essential, although indeterminate for RT planning. The pros and cons of the available techniques have been extensively reported. CONCLUSION: PET/CT has a central place in the planning of radiotherapy for lung cancer and, in particular, for NSCLC assuming a substantial role in the delineation of tumor volume. The development of new radiopharmaceuticals can help overcome the problems related to the disadvantage of FDG to accumulate also in activated inflammatory cells, thus improving tumor characterization and providing new prognostic biomarkers.

6.
Endocr Connect ; 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-32213660

RESUMO

INTRODUCTION AND AIM: Ectopic ACTH secretion (EAS) is mostly secondary to thoracic/abdominal neuroendocrine tumours (NETs), or small cell-lung carcinoma (SCLC). We studied the diagnostic accuracy of computed tomography (CT) with 68Ga-Dota derivatives (68Ga-SSTR) positron emission tomography (PET) in localizing ACTH-secreting tumor in patients with EAS. MATERIALS AND METHODS: 68Ga-SSTR-PET/CT was performed and compared with the nearest enhanced CT in 18 cases (16 primary and 2 recurrent neoplasms). Unspecific, indeterminate and false positive uptakes were assessed using conventional imaging, follow-up or histology. RESULTS: We diagnosed 13 thoracic (9 primary and 2 recurrent bronchial carcinoids, 2 SCLCs) and 1 abdominal (pancreatic NET) tumors. 8 ACTH-secreting tumors were promptly identified at EAS diagnosis ('overt', 4 pulmonary carcinoids with 2 recurrences, and 2 SCLC); 6 EAS have been discovered during the subsequent follow-up ('covert', 5 bronchial carcinoids and 1 pancreatic NET). At the time of EAS diagnosis, imaging was able to correctly detect the ACTH-secreting tumour in 8/18 cases (6 new diagnosis and 2 recurrences). During the follow-up, 6 out of initially 10 'occult' cases became 'covert'. At last available follow-up, CT and 68Ga-SSTR-PET/CT were able to diagnose respectively 11/18 and 12/18 ACTH-secreting tumours (respectively 11/14 and 12/14 considering only overt and covert cases). 4 cases have never been localized by conventional or nuclear imaging ('occult' EAS), despite an average follow up of 5 years. CONCLUSIONS: The 68Ga-SSTR-PET/CT is useful in localizing EAS, especially to enhance positive prediction of the suggestive CT lesions and to detect occult neoplasms.

7.
Interact Cardiovasc Thorac Surg ; 30(4): 593-596, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32003806

RESUMO

Although 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) scan has been generally validated in the staging of malignant pleural mesothelioma (MPM), its diagnostic and prognostic performances are not clearly established. Aiming to identify possible factors causing 18F-fluorodeoxyglucose PET/CT false-negative results and influencing prognosis in MPM patients, we analysed clinical, radiometabolic and pathological features in 141 MPM patients who underwent diagnostic 18F-fluorodeoxyglucose PET/CT scan (January 2009-July 2018) at 2 high-volume institutions. The Fisher's exact test and the Cox model were used in statistical analysis. Overall detection rate was 88.3% with 16 patients (11.6%) presenting with a standardized uptake value (SUV) max <2.5 (PET-negative). PET-negative cases were more frequently detected in older patients (P = 0.027) and early-stage tumours (33.3% false-negative in stage I and 40.0% false-negative in T1-tumours, with P = 0.014 both). Mean SUVmax value was higher in sarcomatoid (11.8 ± 4.6) and biphasic MPM (9.3 ± 7.0), rather than in epithelioid MPM (6.9 ± 3.8, P < 0.001). Concerning overall survival, SUVmax (both as continuous and as categorical variable) was found to be a prognostic factor, in addition to stage (P = 0.032) and histology (P = 0.014) as confirmed by multivariable analysis (hazard ratio 2.65, confidence interval 1.23-5.70; P < 0.001). In the light of such results, we highlight that a low fluorodeoxyglucose uptake might be observed in more than 10% MPMs, especially in early-stage tumours affecting elderly patients. Furthermore, high SUVmax values significantly correlated with a worse prognosis.


Assuntos
Fluordesoxiglucose F18/farmacologia , Neoplasias Pulmonares/diagnóstico , Mesotelioma/diagnóstico , Estadiamento de Neoplasias/métodos , Neoplasias Pleurais/diagnóstico , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Idoso , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Prognóstico , Compostos Radiofarmacêuticos/farmacologia , Reprodutibilidade dos Testes
8.
J Clin Endocrinol Metab ; 105(3)2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31633759

RESUMO

CONTEXT: We investigated the role of Gallium 68 dodecanetetraacetic acid Tyr3-octreotide (68Ga-DOTATOC) positron emission tomography/computed tomography (PET/CT) in detecting somatostatin receptors (SSTRs) in 19 patients with metastatic adrenocortical carcinoma (ACC) and explored the activity of yttrium-90/lutetium-177 (90Y/177Lu-DOTATOC) peptide receptor radionuclide therapy (PRRT). CASE DESCRIPTION AND METHODS: 68Ga uptake in metastatic sites was scored in terms of intensity and anatomical uptake distribution of standard uptake value (SUV). Tissue expression of SSTR2A and SSTR5 was also evaluated by immunohistochemistry (IHC) on primary tumors. Eight (42%) patients displayed radiometabolic uptake of any-grade intensity with focal and limited distribution. Two (11%) patients displayed strong uptake in multiple lesions and were treated with PRRT. Both obtained an overall disease control lasting 4 and 12 months, respectively. CONCLUSIONS: ACC can express SSTRs as detected by IHC and 68Ga-DOTATOC PET. SSTRs-based PRRT may represent a potential treatment opportunity for a minority of patients with advanced ACC. This treatment modality deserves further investigation.


Assuntos
Neoplasias do Córtex Suprarrenal/radioterapia , Carcinoma Adrenocortical/radioterapia , Octreotida/análogos & derivados , Receptores de Somatostatina/metabolismo , Radioisótopos de Ítrio/uso terapêutico , Neoplasias do Córtex Suprarrenal/metabolismo , Neoplasias do Córtex Suprarrenal/patologia , Carcinoma Adrenocortical/metabolismo , Carcinoma Adrenocortical/patologia , Adulto , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Octreotida/uso terapêutico , Prognóstico , Estudos Prospectivos
9.
Clin Exp Rheumatol ; 38 Suppl 124(2): 23-30, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31573481

RESUMO

OBJECTIVES: To investigate serum levels of a panel of angiogenic inducers (VEGF, FGF-2, Angiopoietin 1, -2, soluble VCAM-1) and inhibitors (angiostatin, endostatin, pentraxin-3) in patients with giant cell arteritis (GCA) and Takayasu's arteritis (TAK), in order to gain further insights into the molecular mechanisms driving angiogenesis dysregulation in large-vessel vasculitis (LVV). METHODS: Sera were obtained from 33 TAK patients and 14 GCA patients and from two groups of age-matched normal controls (NC). Disease activity was assessed using 18F-FDG PET/CT and clinical indices including NIH/Kerr criteria and ITAS. Angiogenic and anti-angiogenic factor serum levels were evaluated using commercial ELISA kits. Pentraxin 3 (PTX3) serum levels were evaluated by non-commercial ELISA, as already described. RESULTS: Among the angiogenic factors, only VEGF serum levels were significantly higher in TAK patients compared to NC. No difference was found between angiogenic factor levels in GCA patients compared to those detected in NC. Anti-angiogenic factor (Angiostatin, Endostatin, PTX3) serum levels were significantly higher in both GCA and TAK patients compared to NC. Significant associations were observed between VEGF and PTX3 levels and disease activity evaluated using PET scan and clinical indices. Cluster analysis based on PET scan scores in TAK patients showed significant ordered differences in VEGF and angiostatin serum levels. Indeed, we noted a progressive increase of VEGF and angiostatin from NC to the cluster including patients with the highest and more diffuse scan positivity. CONCLUSIONS: Our overall results demonstrate a circulating molecular profile characterised by a prevailing expression of anti-angiogenic soluble factors.


Assuntos
Proteínas Angiogênicas/sangue , Proteínas Angiostáticas/sangue , Arterite de Células Gigantes/sangue , Arterite de Takayasu/sangue , Angiopoietina-1 , Angiopoietina-2 , Angiostatinas , Proteína C-Reativa , Endostatinas , Fator 2 de Crescimento de Fibroblastos , Humanos , Neovascularização Patológica/sangue , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Tomografia por Emissão de Pósitrons , Componente Amiloide P Sérico , Molécula 1 de Adesão de Célula Vascular , Fator A de Crescimento do Endotélio Vascular
10.
Clin Cancer Res ; 26(2): 373-383, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31645353

RESUMO

PURPOSE: Early response to ABVD, assessed with interim FDG-PET (iPET), is prognostic for classical Hodgkin lymphoma (cHL) and supports the use of response adapted therapy. The aim of this study was to identify a gene-expression profile on diagnostic biopsy to predict iPET positivity (iPET+). EXPERIMENTAL DESIGN: Consecutive untreated patients with stage I-IV cHL who underwent iPET after two cycles of ABVD were identified. Expression of 770 immune-related genes was analyzed by digital expression profiling (NanoString Technology). iPET was centrally reviewed according to the five-point Deauville scale (DS 1-5). An iPET+ predictive model was derived by multivariate regression analysis and assessed in a validation set identified using the same inclusion criteria. RESULTS: A training set of 121 and a validation set of 117 patients were identified, with 23 iPET+ cases in each group. Sixty-three (52.1%), 19 (15.7%), and 39 (32.2%) patients had stage I-II, III, and IV, respectively. Diagnostic biopsy of iPET+ cHLs showed transcriptional profile distinct from iPET-. Thirteen genes were stringently associated with iPET+. This signature comprises two functionally stromal-related nodes. Lymphocytes/monocytes ratio (LMR) was also associated to iPET+. In the training cohort a 5-gene/LMR integrated score predicted iPET+ [AUC, 0.88; 95% confidence interval (CI), 0.80-0.96]. The score achieved a 100% sensitivity to identify DS5 cases. Model performance was confirmed in the validation set (AUC, 0.68; 95% CI, 0.52-0.84). Finally, iPET score was higher in patients with event versus those without. CONCLUSIONS: In cHL, iPET is associated with a genetic signature and can be predicted by applying an integrated gene-based model on the diagnostic biopsy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/genética , Fluordesoxiglucose F18/metabolismo , Doença de Hodgkin/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Transcriptoma , Adulto , Biomarcadores Tumorais/metabolismo , Bleomicina/administração & dosagem , Estudos de Coortes , Dacarbazina/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Doença de Hodgkin/diagnóstico por imagem , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Compostos Radiofarmacêuticos/metabolismo , Vimblastina/administração & dosagem
11.
Comput Methods Programs Biomed ; 185: 105153, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31678792

RESUMO

BACKGROUND AND OBJECTIVES: Malignant lymphomas are cancers of the immune system and are characterized by enlarged lymph nodes that typically spread across many different sites. Many different histological subtypes exist, whose diagnosis is typically based on sampling (biopsy) of a single tumor site, whereas total body examinations with computed tomography and positron emission tomography, though not diagnostic, are able to provide a comprehensive picture of the patient. In this work, we exploit a data-driven approach based on multiple-instance learning algorithms and texture analysis features extracted from positron emission tomography, to predict differential diagnosis of the main malignant lymphomas subtypes. METHODS: We exploit a multiple-instance learning setting where support vector machines and random forests are used as classifiers both at the level of single VOIs (instances) and at the level of patients (bags). We present results on two datasets comprising patients that suffer from four different types of malignant lymphomas, namely diffuse large B cell lymphoma, follicular lymphoma, Hodgkin's lymphoma, and mantle cell lymphoma. RESULTS: Despite the complexity of the task, experimental results show that, with sufficient data samples, some cancer subtypes, such as the Hodgkin's lymphoma, can be identified from texture information: in particular, we achieve a 97.0% of sensitivity (recall) and a 94.1% of predictive positive value (precision) on a dataset that consists in 60 patients. CONCLUSIONS: The presented study indicates that texture analysis features extracted from positron emission tomography, combined with multiple-instance machine learning algorithms, can be discriminating for different malignant lymphomas subtypes.

12.
J Clin Med ; 8(5)2019 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-31091813

RESUMO

BACKGROUND: Molecular nuclear medicine plays a pivotal role for diagnosis in a preclinical phase, in genetically susceptible patients, for radio-guided surgery, for disease relapse evaluation, and for therapy decision-making and follow-up. This is possible thanks to the development of new radiopharmaceuticals to target specific biomarkers of infection, inflammation and tumour immunology. METHODS: In this review, we describe the use of specific radiopharmaceuticals for infectious and inflammatory diseases with the aim of fast and accurate diagnosis and treatment follow-up. Furthermore, we focus on specific oncological indications with an emphasis on tumour immunology and visualizing the tumour environment. RESULTS: Molecular nuclear medicine imaging techniques get a foothold in the diagnosis of a variety of infectious and inflammatory diseases, such as bacterial and fungal infections, rheumatoid arthritis, and large vessel vasculitis, but also for treatment response in cancer immunotherapy. CONCLUSION: Several specific radiopharmaceuticals can be used to improve diagnosis and staging, but also for therapy decision-making and follow-up in infectious, inflammatory and oncological diseases where immune cells are involved. The identification of these cell subpopulations by nuclear medicine techniques would provide personalized medicine for these patients, avoiding side effects and improving therapeutic approaches.

13.
Sci Rep ; 9(1): 3376, 2019 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-30833583

RESUMO

MiRNAs are single stranded RNAs of 18-22 nucleotides. They are promising diagnostic and prognostic markers for several pathologies including tumors, neurodegenerative, cardiovascular and autoimmune diseases. In the present work the development and characterization of anti-miRNA radiolabeled probes based on peptide nucleic acids (PNAs) for potential non-invasive molecular imaging in vivo of giant cell arteritis are described. MiR-146a and miR-146b-5p were selected as targets because they have been found up-regulated in this disease. Anti-miR and scramble PNAs were synthesized and linked to carboxyfluorescein or DOTA. DOTA-anti-miR PNAs were then labelled with copper-64 (64Cu) to function as non-invasive molecular imaging tools. The affinity of the probes for the targets was assessed in vitro by circular dichroism and melting temperature. Differential uptake of fluorescein and 64Cu labeled anti-miRNA probes was tested on BCPAP and A549 cell lines, expressing different levels of miR-146a and -146b-5p. The experiments showed that the anti-miR-146a PNAs were more effective than the anti-miR-146b-5p PNAs. Anti-miR-146a PNAs could bind both miR-146a and miR-146b-5p. The uptake of fluorescein and 64Cu labeled anti-miR-146a PNAs was higher than that of the negative control scramble PNAs in miRNA expressing cells in vitro. 64Cu-anti-miR-146a PNAs might be further investigated for non-invasive PET imaging of miR-146 overexpressing diseases.

14.
Phys Med ; 57: 153-159, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30738519

RESUMO

BACKGROUND: At present activity quantification is one of the most critical step in dosimetry calculation, and Partial Volume Effect (PVE) one of the most important source of error. In recent years models based upon phantoms that incorporate hot spheres have been used to establish recovery models. In this context the goal of this study was to point out the most critical issues related to PVE and to establish a model closer to a biological imaging environment. METHODS: Two different phantoms, filled with a 177Lu solution, were used to obtain the PVE Recovery Coefficients (RCs): a phantom with spherical inserts and a phantom with organ-shaped inserts. Two additional phantoms with inserts of various geometrical shapes and an anthropomorphic phantom were acquired to compare the real activities to predicted values after PVE correction. RESULTS: The RCs versus volume of the inserts produced two different curves, one for the spheres and one for the organs. After PVE correction, accuracy on activity quantification averaged over all inserts of three test phantoms passed from -26% to 1.3% (from 26% to 10% for absolute values). CONCLUSION: RCs is a simple method for PVE correction easily applicable in clinical routine. The use of two different models for organs and lesions has permitted to closely mimic the situation in a living subject. A marked improvement in the quantification of activity was observed when PVE correction was adopted, even if further investigations should be performed for more accurate models of PVE corrections.


Assuntos
Octreotida/análogos & derivados , Radioterapia , Receptores de Somatostatina/metabolismo , Tomografia Computadorizada de Emissão de Fóton Único , Humanos , Processamento de Imagem Assistida por Computador , Imagens de Fantasmas
15.
Interact Cardiovasc Thorac Surg ; 28(6): 957-960, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-30753507

RESUMO

Few data are available about radio-receptorial positron emission tomography (PET) results by the use of 68Ga-DOTA-peptides in pulmonary carcinoid tumours. In this study, we retrospectively analysed 68Ga-DOTATOC/PET and 18Fluorodeoxyglucose (FDG) PET diagnostic performances in 62 pulmonary carcinoids (occurring in 57 patients) and interrelationship with histological features. All patients underwent at least 1 PET/computed tomography: 26 patients received 68Ga-DOTATOC, 52 patients had 18F-FDG and 20 patients received both techniques. There were 55 typical carcinoids and 7 atypical carcinoids. 68Ga-DOTATOC/PET recorded an 88.4% overall detection rate (DR) (meanSUVmax: 15.5); 18F-FDG/PET a DR of 53.8% (meanSUVmax: 3.2). When adopted a maximum standardized uptake value-threshold of 1.5, DRs of 68Ga-DOTATOC and 18F-FDG/PET increased to 100% and 80.8%, respectively. Moreover, DRs in both techniques vary considerably according to histology with 68Ga-DOTATOC/PET having better performances in typical carcinoids than in atypical carcinoids (DR: 91.7% vs 50.0%, P = 0.076). We also observed a significant correlation between a low number of mitoses (<2/10 high-power field) and 68Ga-DOTATOC/PET-positivity (P = 0.004), and an association trend (P = 0.076) between necrosis and 68Ga-DOTATOC/PET-negativity. In conclusion, 68Ga-DOTATOC had better diagnostic performances than 18F-FDG/PET in detecting pulmonary carcinoids. DRs of both techniques remarkably varied according to histology with 68Ga-DOTATOC/PET performing at its best in typical carcinoids, whereas 18F-FDG/PET did the same in atypical carcinoids.68Ga-DOTATOC/PET results were presumably associated with the number of mitoses and the presence of necrosis.


Assuntos
Tumor Carcinoide/diagnóstico , Fluordesoxiglucose F18/farmacologia , Neoplasias Pulmonares/diagnóstico , Pulmão/diagnóstico por imagem , Octreotida/análogos & derivados , Compostos Organometálicos/farmacologia , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Idoso , Tumor Carcinoide/cirurgia , Feminino , Radioisótopos de Gálio , Humanos , Pulmão/cirurgia , Neoplasias Pulmonares/cirurgia , Masculino , Octreotida/farmacologia , Pneumonectomia/métodos , Compostos Radiofarmacêuticos/farmacologia , Reprodutibilidade dos Testes , Estudos Retrospectivos
16.
Eur J Nucl Med Mol Imaging ; 46(5): 1102-1110, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30637501

RESUMO

PURPOSE: REASSURE is a global, prospective, non-interventional study to assess long-term safety of radium-223 in patients with bone metastatic castration-resistant prostate cancer. Here we report an interim analysis of patients according to previous use of chemotherapy. METHODS: Radium-223 was administered in routine clinical practice. Interim safety analysis was planned after enrolment of the first 600 patients. Patient characteristics and safety data by previous administration of chemotherapy (docetaxel and/or cabazitaxel) were investigated. RESULTS: This interim analysis included 583 patients. Median duration of observation was 7 months (range, 0-20). Nineteen patients treated with concomitant chemotherapy were excluded, 564 (97%) were eligible for exploratory analysis according to prior use of chemotherapy; 190 (34%) had previously received and completed chemotherapy, and 374 (66%) had not. In the prior versus no prior chemotherapy group, a higher proportion of patients had an Eastern Cooperative Oncology Group performance status of ≥2 (22% vs 11%) and > 20 metastatic lesions (26% vs 15%), median alkaline phosphatase (162.0 vs 115.0 U/L) and prostate-specific antigen (132.0 vs 40.2 ng/mL) levels were higher, and a lower proportion completed 6 radium-223 injections (45% vs 63%). Drug-related treatment-emergent adverse events (TEAEs) occurred in 63 and 48%, and haematological drug-related TEAEs in 21 and 9% of patients who had or had not previously received chemotherapy. Four drug-related deaths were reported, all in the prior chemotherapy group. CONCLUSIONS: The short-term safety profile of radium-223 in routine clinical practice was comparable to other clinical studies, irrespective of prior chemotherapy use. Haematological TEAEs occurred more frequently in the prior chemotherapy group, presumably due to decreased bone marrow function as a consequence of more advanced disease and prior exposure to cytotoxic therapy. Patients who had not previously received chemotherapy appeared to have a lower burden of disease at baseline, and a lower proportion discontinued radium-223 treatment.

17.
Semin Arthritis Rheum ; 48(6): 1074-1082, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30424972

RESUMO

OBJECTIVE: To evaluate aortic diameter and predictors of aortic dilatation using 18FDG-PET/CT in a longitudinally followed cohort of patients with large vessel vasculitis (LVV) compared with controls. METHODS: All consecutive patients with LVV who underwent at least 2 PET/CT scans between January 2008 and May 2015 were included. The first and last PET/CT study was evaluated by a radiologist and a nuclear medicine physician. Diameter and FDG uptake of the aorta was measured at 4 different levels: ascending, descending thoracic, suprarenal and infrarenal abdominal aorta. Twenty-nine age- and sex-matched patients with lymphoma who underwent at least 2 PET/CT scans in the same time interval were selected as controls. RESULTS: 93 patients with LVV were included in the study. In the time interval between first and last PET/CT study (median time 31 months), the diameter of the ascending, descending thoracic and suprarenal abdominal aorta significantly increased in LVV patients but not in controls. At last PET/CT, patients with LVV compared with controls had higher diameter of ascending [35.41 (5.54) vs 32.97 (4.11) mm, p = 0.029], descending thoracic [28.42 (4.82) vs 25.72 (3.55) mm, p = 0.007] and suprarenal abdominal aorta, mean [25.34 (7.01) vs 22.16 (3.26) mm, p = 0.005] and more frequently had aortic dilatation [19% vs 3%, p = 0.023]. Significant predictors of aortic dilatation were male sex [OR 7.27, p = 0.001] and, only for GCA, hypertension [OR 6.30, p = 0.031]. Finally, GCA patients with aortic FDG uptake grade 3 at first PET/CT, compared to those with aortic FDG uptake ≤2, had significantly higher aortic diameter. CONCLUSIONS: Patients with LVV are at increased risk of aortic dilatation compared with age- and sex-matched controls. Significant predictors of aortic dilatation are male sex and, only for GCA, hypertension. GCA patients with aortic FDG uptake grade 3 are at increased risk of aortic dilatation.


Assuntos
Aorta/diagnóstico por imagem , Doenças da Aorta/diagnóstico por imagem , Arterite de Células Gigantes/diagnóstico por imagem , Arterite de Takayasu/diagnóstico por imagem , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Fatores de Risco
18.
EJNMMI Res ; 8(1): 64, 2018 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-30032450

RESUMO

BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin tumor. Currently, 18F-fluoro-deoxy-glucose (18F-FDG) PET/CT is the functional imaging modality of choice. Few data are available on the use of 68Ga-somatostatin analogs. The aim of our study was to evaluate and compare the diagnostic performance of 18F-FDG and 68Ga-somatostatin analog PET/CT in MCC patients. RESULTS: Fifteen patients (12 males, 3 females; median age 73 years; range 41-81 years) with histologically proven MCC (4 with unknown primary lesion) who underwent both 18F-FDG and 68Ga-somatostatin analog PET/CT for staging, re-staging, or treatment response assessment were retrospectively evaluated. Results of both studies were qualitatively analyzed and compared on a patient- and lesion-based analysis, using histology or clinical/radiological follow-up as reference standard for final diagnosis. According to final diagnosis, 8/15 patients had at least one MCC lesion and 7/15 had no evidence of disease. On a patient-based analysis, 18F-FDG and 68Ga-somatostatin analogs correctly classified as positive 8/8 (100% sensitivity) patients and as negative 6/7 (85.7% specificity) and 5/7 (71.4% specificity) patients, respectively, with no significant difference. On a lesion-based analysis, 18F-FDG detected 67/75 lesions (89%) and 68Ga-somatostatin analogs 69/75 (92%), with no significant difference. In four patients with unknown primary MCC, both tracers failed to identify the primary MCC site. CONCLUSIONS: Our preliminary data suggest that 18F-FDG and 68Ga-somatostatin analog PET/CT provide good and equivalent diagnostic performance, adding interesting insights into the complex MCC biology. However, these results do not suggest that 18F-FDG PET/CT should be replaced by 68Ga-somatostatin receptor imaging, which should be performed in addition, according to clinical indication, to the perspective of "personalized medicine."

19.
Clin Exp Rheumatol ; 36 Suppl 111(2): 99-106, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29799393

RESUMO

OBJECTIVES: To compare patterns of vascular involvement using 18F-fluorodeoxyglucose-positron emission tomography computed tomography (FDG PET/CT) in patients with giant cell arteritis (GCA) and Takayasu's arteritis (TAK). METHODS: A total of 130 consecutive 18F-FDG PET/CT scans performed during the disease course for evaluating disease activity in 15 GCA and 13 TAK patients were retrospectively examined by two nuclear physicians blinded to clinical data. Standardised uptake values (SUVmax) in 14 vascular districts including all the aortic segments and the main tributaries were measured. The average SUVmax value for each vascular district was also calculated. Principal component analysis (PCA) and agglomerative hierarchical cluster analysis (CA) were used to explore distribution patterns of vascular FDG uptake. RESULTS: The aortic segments showed the highest SUV max values among the different districts in both GCA and TAK. SUV max values measured in the different districts were significantly higher in GCA compared to TAK, except for the axillary arteries. Regarding thoracic and abdominal aorta, ascending aorta and aortic arch had the highest correlation in both vasculitis (p<0.0001). CA confirmed that carotid, axillary, subclavian, iliac and femoral arteries clustered with their contralateral counterpart in both vasculitis. The 3 components of thoracic aorta clustered with abdominal aorta in TAK, while aortic arch clustered only with ascending aorta, and descending and abdominal aorta grouped together with iliac and femoral arteries in GCA. PCA analysis identified 3 different components for TAK and GCA explaining 72% and 71% of the total variance respectively in these two vasculitis. Confirming CA, a component including the entire aortic district was identified in TAK, but not in GCA. Similar results in PCA using averaged data were observed. CONCLUSIONS: Strong similarities, but also a subtle skewing in terms of distribution patterns of arterial involvement assessed by SUVmax values were observed between GCA and TAK.


Assuntos
Aortite/diagnóstico por imagem , Doenças das Artérias Carótidas/diagnóstico por imagem , Arterite de Células Gigantes/diagnóstico por imagem , Arterite de Takayasu/diagnóstico por imagem , Adulto , Idoso , Aorta Abdominal/diagnóstico por imagem , Aorta Torácica/diagnóstico por imagem , Aortite/etiologia , Artéria Axilar/diagnóstico por imagem , Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/etiologia , Análise por Conglomerados , Feminino , Artéria Femoral/diagnóstico por imagem , Fluordesoxiglucose F18 , Humanos , Artéria Ilíaca/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Análise de Componente Principal , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Artéria Subclávia/diagnóstico por imagem
20.
Semin Nucl Med ; 48(3): 277-290, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29626944

RESUMO

Rheumatic disorders comprise a number of diseases that range from benign, mildly symptomatic degenerative disease to severe systemic disorders such as giant-cell vasculitis with dramatic consequences such as acute blindness. The former is relatively common, whereas the latter is rare. In between, commonly encountered disorders such as rheumatoid arthritis and the various spondyloarthritides, with or without peripheral enthesitis, are daily challenges for the caring physician. Clinical evaluation is of utmost importance and is constantly described under the form of specialist guidelines in all parts of the world. Objective assessment of inflammatory arthritis and related disorders is of interest both for the care of the individual patient and for the assessment of the effects of the many novel experimental therapies proposed in this field, most of them being very expensive. High-resolution ultrasound, CT and spectral CT, MRI using various sequences, and molecular imaging using either gamma camera imaging (including SPECT-CT) or PET-CT are all proposed for a better assessment of these diseases. This review focuses on the several nuclear medicine techniques that are or may become useful to helping provide better patient care in this field and is mainly oriented to inflammatory rheumatic disorders, excluding mechanical degenerative diseases.


Assuntos
Artrite Reumatoide/complicações , Artrite Reumatoide/diagnóstico por imagem , Imagem Molecular/métodos , Humanos , Medicina de Precisão
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