Scher H.I.,Genitourinary Oncology Service |
Anand A.,Genitourinary Oncology Service |
Rathkopf D.,Genitourinary Oncology Service |
Shelkey J.,Genitourinary Oncology Service |
And 15 more authors.
The Lancet | Year: 2010
Background MDV3100 is an androgen-receptor antagonist that blocks androgens from binding to the androgen receptor and prevents nuclear translocation and co-activator recruitment of the ligand-receptor complex. It also induces tumour cell apoptosis, and has no agonist activity. Because growth of castration-resistant prostate cancer is dependent on continued androgen-receptor signalling, we assessed the antitumour activity and safety of MDV3100 in men with this disease. Methods This phase 1-2 study was undertaken in fi ve US centres in 140 patients. Patients with progressive, metastatic, castration-resistant prostate cancer were enrolled in dose-escalation cohorts of three to six patients and given an oral daily starting dose of MDV3100 30 mg. The fi nal daily doses studied were 30 mg (n=3), 60 mg (27), 150 mg (28), 240 mg (29), 360 mg (28), 480 mg (22), and 600 mg (3). The primary objective was to identify the safety and tolerability profi le of MDV3100 and to establish the maximum tolerated dose. The trial is registered with ClinicalTrials.gov, number NCT00510718. Findings We noted antitumour eff ects at all doses, including decreases in serum prostate-specifi c antigen of 50% or more in 78 (56%) patients, responses in soft tissue in 13 (22%) of 59 patients, stabilised bone disease in 61 (56%) of 109 patients, and conversion from unfavourable to favourable circulating tumour cell counts in 25 (49%) of the 51 patients. PET imaging of 22 patients to assess androgen-receptor blockade showed decreased18F-fl uoro-5α-dihydrotestosterone binding at doses from 60 mg to 480 mg per day (range 20-100%). The median time to progression was 47 weeks (95% CI 34-not reached) for radiological progression. The maximum tolerated dose for sustained treatment (>28 days) was 240 mg. The most common grade 3-4 adverse event was dose-dependent fatigue (16 [11%] patients), which generally resolved after dose reduction. Interpretation We recorded encouraging antitumour activity with MDV3100 in patients with castration-resistant prostate cancer. The results of this phase 1-2 trial validate in man preclinical studies implicating sustained androgenreceptor signalling as a driver in this disease. Funding Medivation, the Prostate Cancer Foundation, National Cancer Institute, the Howard Hughes Medical Institute, Doris Duke Charitable Foundation, and Department of Defense Prostate Cancer Clinical Trials Consortium.
Feola M.,Cardiovascular Rehabilitation Heart Failure Unit |
Garrone O.,Nuclear Medicine Service |
Occelli M.,Nuclear Medicine Service |
Francini A.,Nuclear Medicine Service |
And 4 more authors.
International Journal of Cardiology | Year: 2011
Anthracyclines are among the most active drugs in breast cancer patients. We planned to evaluate the early and 2-year modification of left ventricular ejection fraction (LVEF) and the effects of chemotherapy on troponin I and neurohormonal assessment. Methods: Patients with early breast cancer surgically treated and eligible to adjuvant chemotherapy were enrolled. All patients underwent clinical assessment, radionuclide ventriculography, troponin I and brain natriuretic peptide (BNP) measurements at baseline and one-month (T1), one year (T2) and 2-year (T3) after chemotherapy. Reductions of LVEF ≥ 10% or an overt heart failure were considered cardiovascular events. Results: 53 patients, 52 females and 1 male, age 55.3 years were included and followed at T3. A significant reduction of LVEF was observed (from 62 ± 5.5% to 59.3 ± 8.6%, p = 0.04) at T3; BNP increased (from 33.4 ± 41.5 pg/ml to 62.7 ± 94.7 pg/ml, p = 0.005) at T1. Troponin I augmented at T1 (from 0.006 ± 0.01 ng/ml to 0.05 ± 0.04 ng/ml, p = 0.0001) but normalized at T2 (0.005 ± 0.08 ng/ml; p = 0.9). Only baseline BNP was nearly to be significantly correlated with T3 LVEF (p = 0.07 HR 0.96-1) at multivariate analysis. In 13/53 patients (32.1%) LVEF showed ≥ 10% reduction at T3 (group A); in 40/53 patients (67.9%) LVEF was unchanged (group B). Patients in group A demonstrated higher baseline plasma BNP (p = 0.02) and lower haemoglobin concentration (p = 0.007) compared to patients in group B. Conclusions: LVEF and BNP modified early after anthracycline chemotherapy and LVEF did not recover at T3. In patients who developed left ventricular systolic dysfunction, a subclinical activation of neurohormonal profile was observed. © 2009 Elsevier Ireland Ltd.
Charest M.,Nuclear Medicine Service |
Sirois C.,Hopital du Sacre Coeur de Montreal |
Cartier Y.,Diagnostic Radiology Service |
Rousseau J.,Hopital du Sacre Coeur de Montreal
British Journal of Radiology | Year: 2012
The differential diagnosis for intense hypermetabolic mediastinal lesions on positron emission tomography (PET) could benefit from the combined morphological and metabolic information present in a fluorodeoxyglucose (FDG) PET/CT study. We report a case of an infected tracheal diverticulum mimicking an FDG-avid malignancy in a patient with a history of chronic lymphoproliferative disease. We review the literature for a systematic approach in the differential diagnosis of cystic mediastinal lesions. The embryological development of the normal tracheobronchial tree is reviewed, followed by a presentation of various congenital and acquired mediastinal lesions. The characteristic CT findings are described for each lesion and the avidity for FDG on PET is mentioned when references are available. This case emphasises that complicated benign processes should be considered in the differential diagnosis of an FDG-avid mediastinal lesion, even in subgroups of patients with significant risk factors for malignancy. © 2012 The British Institute of Radiology.
Galluzzi S.,Irccs Instituto Centro San Giovanni Of Dio Fatebenefratelli |
Geroldi C.,Irccs Instituto Centro San Giovanni Of Dio Fatebenefratelli |
Amicucci G.,Service of Anesthesiology |
Bocchio-Chiavetto L.,Irccs Instituto Centro San Giovanni Of Dio Fatebenefratelli |
And 7 more authors.
Journal of Neurology | Year: 2013
The aim of this study is to support the use of biomarkers in the diagnosis of mild cognitive impairment (MCI) due to Alzheimer’s disease (AD) according to the revised NIA-AA diagnostic criteria. We compared clinical features and conversion to AD and other dementias among groups of MCI patients with different abnormal biomarker profiles. In this study, we enrolled 58 patients with MCI, and for each of them AD biomarkers (CSF Abeta42 and tau, temporoparietal hypometabolism on 18F-FDG PET, and hippocampal volume) were collected. Patients were divided into three groups: (i) no abnormal biomarker, (ii) AD biomarker pattern (including three subgroups of early = only abnormal Abeta42, intermediate = abnormal Abeta42 and FDG PET or tau, and late = abnormal Abeta42, FDG PET or tau, and HV), and (iii) any other biomarker combination. MCI patients with AD biomarker pattern had lower behavioural disturbances than patients with any other biomarker combination (p<0.0005). This group also showed lower performance on verbal and nonverbal memory than the other two groups (p = 0.07 and p = 0.004, respectively). Within the three subgroups with AD biomarker patterns we observed a significant trend toward a higher rate of conversion to dementia (p for trend = 0.006). With regard to dementia conversion, 100 % of patients with an AD biomarker pattern developed AD, but none of the patients with no abnormal biomarker and 27 % of patients with any other biomarker combination (p = 0.002) did so. We also described some clinical cases representative for each of these three groups. The results of this study provide evidence in favour of the use of biomarkers for the diagnosis of MCI due to AD, in line with recently published research criteria. © Springer-Verlag Berlin Heidelberg 2012.
Mateo L.,Rheumatology Service |
Massuet A.,Magnetic Resonance |
Sola M.,Nuclear Medicine Service |
Perez Andres R.,Radiology |
And 2 more authors.
Clinical Rheumatology | Year: 2011
Brown tumors (BT) are benign focal bone lesions that may appear in the context of primary and secondary hyperparathyroidism (HPT). Involvement of the spine is exceedingly rare. We present a case of brown tumor involving the cervical spine, the third reported in the literature. In the literature review (until August 2010), we found nine cases of spinal BT in primary HPT and 14 cases in secondary HPT. Fifteen patients (65%) had evidence of spinal cord compression. A 34-year-old woman on long-term hemodialysis, with secondary HPT, presented with a 9-month history of persistent neck pain. Radiographs of the cervical spine revealed an expansive osteolytic lesion in the posterior arch of the second cervical vertebra. MR imaging revealed an expansive mass on C2 affecting the vertebral body, odontoid process, right pedicle, laminas, and spinous process; there were no signs of spinal edema. A CT-guided needle biopsy of the lesion showed destruction of trabecular bone, infiltration of the fibroblastic cells, and abundant osteoclast-like multinucleated giant cells with hemorrhage and hemosiderin pigment, and the diagnosis of brown tumor was made. Cervical pain disappeared within a few days of parathyroidectomy, and rapid remineralization of C2 was evident within a few months. BT must always be considered in the context of hyperparathyroidism and osteolytic lesions. Vertebral BT can be particularly devastating due to medullar compression symptoms. Regression or complete disappearance of these lesions after parathyroidectomy is common, but prompt surgical decompression is necessary in case of medullar compression symptoms. © 2010 Clinical Rheumatology.
Carrasquillo J.A.,Nuclear Medicine Service |
Carrasquillo J.A.,Cornell University |
Chen C.C.,U.S. National Institutes of Health
Seminars in Oncology | Year: 2010
Neuroendocrine tumors (NET) are a heterogeneous group of tumors that arise from neuroendocrine cells. These tumors may arise from various organs, including lung, thymus, thyroid, stomach, duodenum, small bowel, large bowel, appendix, pancreas, adrenal, and skin. Most are well differentiated and have the ability to produce biogenic amines and various hormones. NET usually occur sporadically but they also be associated with various familial syndromes. For the vast majority of NET, surgical resection is the treatment of choice whenever feasible. Localization of NET prior to surgery and for staging and follow-up relies on both anatomic and functional imaging modalities. In fact, the unique secretory characteristics of these tumors lend themselves to imaging by molecular imaging modalities, which can target specific metabolic pathways or receptors. Neuroendocrine cells have a variety of such target receptors and pathways for which radiopharmaceuticals have been developed, including [ 123I/131I]-metaiodobenzylguanidine (MIBG), [ 111In]pentetreotide, [68Ga] somatostatin analogs, [ 18F] fluorodeoxyglucose (FDG), [11C/18F] dihydroxyphenylalanine (DOPA), [11C] 5-hydroxytryptophan (5-HTP) 99mTc pentavalent dimercaptosuccinic acid ([99mTc] (V) DMSA, and [18F] fluorodopamine (FDA). Here, we review the molecular imaging approaches for NET using various radiopharmaceuticals. © 2010 Elsevier Inc. All rights reserved.
Liu Y.,Nuclear Medicine Service
AIDS Research and Treatment | Year: 2012
Patients with HIV infection often have generalized lymphadenopathy and/or other lymphoid proliferation and are at significantly increased risk for lymphoma. This study retrospectively evaluated the diagnostic value of concurrent nasopharyngeal lesion and lymphadenopathy on positron emission tomography-computed tomography (PET-CT) with fluorine-18 fluorodeoxyglucose (FDG PET-CT) imaging. The eligible cases were from patients with HIV infection and lymphadenopathy and referred for FDG PET-CT to evaluate lymphoma or other malignancies prior to pathological investigation. FDG PET-CT images and interpretation reports were correlated with clinical information and pathological diagnoses. Among 22 eligible patients, FDG avid nasopharyngeal lesions were incidentally noted in 7 on PET-CT imaging, and all had lymphomas diagnosed with subsequent biopsies (6 diffuse large B-cell lymphomas and 1 Hodgkin's lymphoma). In the remaining 15 patients with adenopathy but no visible nasopharyngeal lesion or uptake on PET-CT imaging, 9 had biopsies and lymphomas were diagnosed in 4. The patients with FDG avid retroperitoneal or intra-abdominal lymphadenopathy had a greater possibility of lymphoma, compared to those with adenopathy localized only in the upper torso. Coexistent FDG avid nasopharyngeal lesion and generalized lymphadenoapthy on PET-CT imaging are indicative of a malignant lymphoma rather than benign lymphproliferative disease or nasopharyngeal carcinoma. © 2012 Yiyan Liu.
Liu Y.,Nuclear Medicine Service
World Journal of Clinical Oncology | Year: 2014
Fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) is not indicated or recommended in the initial staging of early breast cancer. Although it is valuable for detecting distant metastasis, providing prognostic information, identifying recurrence and evaluating response to chemotherapy, the role of FDG PET/CT in evaluating locoregional nodal status for initial staging of breast cancer has not yet been well-defined in clinical practice. FDG PET/CT has high specificity but compromised sensitivity for identifying axillary nodal disease in breast cancer. Positive axillary FDG PET/CT is a good predictor of axillary disease and correlates well with sentinel lymph node biopsy (SLNB). FDG PET/CT may help to identify patients with high axillary lymph node burden who could then move directly to axillary lymph node dissection (ALND) and would not require the additional step of SLNB. However, FDG PET/CT cannot replace SLNB or ALND due to unsatisfactory sensitivity. The spatial resolution of PET instruments precludes the detection of small nodal metastases. Although there is still disagreement regarding the management of internal mammary node (IMN) disease in breast cancer, it is known that IMN involvement is of prognostic significance, and IMN metastasis has been associated with higher rates of distant metastasis and lower overall survival rates. Limited clinical observations suggested that FDG PET/CT has advantages over conventional modalities in detecting and uncovering occult extra-axillary especially IMN lesions with upstaging the disease and an impact on the adjuvant management. © 2014 Baishideng Publishing Group Inc. All rights reserved.
Gomez Perales J.L.,University of the Sea |
Garcia Mendoza A.,Nuclear Medicine Service
Applied Radiation and Isotopes | Year: 2015
This work describes the development of a software application for reporting patient radiation dosimetry following radiopharmaceutical administration. The resulting report may be included within the patient's medical records. The application was developed in the Visual Basic programming language. The dosimetric calculations are based on the values given by the International Commission on Radiological Protection (ICRP). The software is available in both Spanish and English and can be downloaded at no cost from www.radiopharmacy.net. © 2015.
Liu Y.,Nuclear Medicine Service
Oncology Letters | Year: 2014
The role of fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET)-computed tomography (CT) in prostate cancer remains controversial due to a limited number of previous clinical investigations. The aim of the present retrospective study was to assess the diagnostic value of FDG PET-CT in prostate cancer, with an emphasis on the detection of metastatic disease. Twenty-five relevant cases of patients with newly diagnosed prostate cancer, referred for staging, or with a history of prostate cancer or recent prostate specific antigen (PSA) relapse, referred for the detection of metastatic disease, were included in the present study. None of the patients had known imaging or pathological evidence of metastatic disease prior to FDG PET-CT, however, the PSA levels had been recorded in all patients in the two months prior to FDG PET-CT imaging. Verification of the FDG PET-CT observations was made by biopsy, regional diagnostic CT and/or whole-body bone scintigraphy. The sensitivity of FDG PET-CT in identifying untreated primary lesions was only 33% (3/9). However, FDG PET-CT detected metastatic disease in six of the nine patients who underwent initial staging. Out of 16 patients with previous treatments and recent PSA relapse, FDG PET-CT successfully identified metastatic diseases in 12 and tumor recurrence within the prostatic fossa of two patients. The difference in the PSA levels was identified to be statistically significant between the FDG PET-CT-positive and -negative subgroups of the 16 restaging patients. The results indicated that FDG PET-CT is not useful for the diagnosis of prostate cancer, but may aid with the detection of metastatic disease in appropriately selected patients.