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An anthraquinone conjugated macrocyclic chelating agent, 2,2',2â³-(10-(2-(9,10-dioxo-9,10-dihydroanthracen-1-ylamino)-2-oxoethyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetic acid or DO3A-Act-AQ, was synthesized by reacting trisubstituted cyclen (DO3A) with 2-chloro-N-(9,10-dioxo-9,10-dihydro-anthracen-1-yl)-acetamide and radiolabeled with (68)GaCl3 in 84% efficiency and a specific activity of 4.62 MBq/nmol. The IC50 value for BMG-1 cells was 0.1 mM, while the same concentration of DO3A-Act-AQ rendered no significant toxicity in HEK cells. The exposure of BMG-1 cells with 0.1 mM DO3A-Act-AQ displayed a time-dependent increase in apoptosis (40.7% at 4 h and 53% at 24 h), and the effect was 2.8- and 3.6-fold % higher as seen in HEK cells. An increase in S-phase cell population suggested S-phase arrest concomitant with induction of apoptosis in BMG-1 cells reaching to 4.5 times after 24 h with respect to control cells. DNA binding studies on CT-DNA (calf thymus) revealed a quenching pattern in the presence of DO3A-Act-AQ (10-70 µM), and the Stern-Volmer quenching constant was 2.4157 × 10(6) L mol(-1), indicative of strong binding with ds-DNA. A decrease in the positive and negative bands of CT-DNA was seen at 278 nm and 240 nm, respectively, on addition of 0.05 mM of DO3A-Act-AQ in CD studies. (68)Ga-DO3A-Act-AQ was stable in vitro in both PBS and human serum for at least 2 h. The in vivo blood kinetics study performed on normal rabbits indicated fast clearance with t1/2(F) = 40 ± 0.3 min and t1/2(S) = 3 h 30 min ± 0.1 min. Ex vivo biodistribution analysis displayed a favorable tumor-to-muscle ratio of 8.4 after 2 h in athymic nude mice xenografted with BMG-1 cells, suggesting the specificity of (68)Ga-DO3A-Act-AQ toward tumors.
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Antraquinonas/uso terapéutico , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/terapia , Compuestos Heterocíclicos con 1 Anillo/uso terapéutico , Animales , Antraquinonas/química , Antraquinonas/farmacología , Antineoplásicos/química , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Dicroismo Circular , Células HEK293 , Compuestos Heterocíclicos con 1 Anillo/química , Compuestos Heterocíclicos con 1 Anillo/farmacología , Humanos , Ratones , Ratones Desnudos , Conejos , Distribución TisularRESUMEN
INTRODUCTION: Positron emission tomography (PET) imaging with F-18 fluorodeoxyglucose (FDG) has been used to identify characteristic patterns of regional glucose metabolism in patients with idiopathic Parkinson's disease (IPD) and the atypical parkinsonian syndromes of progressive supranuclear palsy (PSP), multiple system atrophy (MSA), and corticobasal syndrome (CBS). We undertook this study to assess the utility of fluorodeoxyglucose-PET in the differential diagnosis of individual patients with clinical parkinsonism. "Visual" and "computer-supported" reading of the fluorodeoxyglucose-PET scans were used for image interpretation and compared with each other. METHODS: One hundred thirty-six parkinsonian patients were referred from movement disorder clinics in specialty neurology centers for the fluorodeoxyglucose-PET study. Imaging-based diagnosis was obtained by visual assessment of individual scans by a PET physician blinded to the clinical diagnosis and also by computer-assisted interpretation using statistical parametric mapping (SPM) analysis. The results were compared with a 2-year follow-up clinical assessment made by a movement disorder specialist. RESULTS: Concordance of visual evaluation of fluorodeoxyglucose-PET with clinical diagnosis was achieved in 91.7% of patients scanned, 97.6% IPD, 80% MSA, 76.6% PSP, and 100% CBS. Blinded computer assessment using SPM was concordant with the clinical diagnosis in 91% of cases evaluated (90.4% IPD, 80% MSA, 93.3% PSP, and 100% CBS). CONCLUSIONS: Fluorodeoxyglucose-PET performed at the time of initial referral for parkinsonism is useful for the differential diagnosis of IPD, PSP, MSA, and CBS. Computer-assisted methods can be used for objective evaluation especially when expert readers are not available.
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Fluorodesoxiglucosa F18 , Trastornos Parkinsonianos/diagnóstico por imagen , Trastornos Parkinsonianos/epidemiología , Tomografía de Emisión de Positrones/métodos , Tomografía de Emisión de Positrones/estadística & datos numéricos , Diagnóstico Diferencial , Femenino , Humanos , India/epidemiología , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Prevalencia , Radiofármacos , Reproducibilidad de los Resultados , Medición de Riesgo , Sensibilidad y EspecificidadRESUMEN
Objective: Spinal cord injury (SCI) extensively impacts the sensorimotor reorganization in the brain. The effects can be both anatomical and functional. To date, not many studies using 18F-Fluoro-2-Deoxyglucose positron emission tomography (18F-FDG PET) to evaluate metabolic changes in the brain are done. Understanding such changes is crucial for developing clinical management and evidence-based rehabilitation strategies for these patients. Subjects and Methods: In this study, we compared 18F-FDG PET imaging of 6 SCI patients with complete paraplegia and 19 controls. Statistical parametric mapping software was utilized to compare the images on a voxel to voxel basis (significance level P < 0.05 and clusters having >50 voxels). Results: The study showed raised metabolism in supplementary motor areas, comprehension centers, some areas in the parietal and temporal lobe, putamen and cerebellum while reduced metabolic uptake in areas like anterior cingulate gyrus, hippocampus and sensory cortical areas when SCI patients were compared against healthy controls. The frontal lobe showed varied results where certain regions showed higher metabolism while the others showed lower in patients compared with controls. Conclusion: Cerebral deafferentation or disuse atrophy can be linked with reduced metabolism while raised uptake can be associated with initiation and planning of movement and cognitive changes in the brain posttrauma.
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OBJECTIVES: The purpose of this study was to evaluate the performance of F-fluorodeoxy-D-glucose (FDG)-PET/computed tomography (CT) and contrast-enhanced CT (CECT) in the detection and characterization of hepatic metastases. METHODS: Forty-five patients harboring an extrahepatic primary malignancy, with suspected hepatic metastases on clinical or ultrasonographic examination were enroled prospectively. Each patient underwent contrast-enhanced abdominal CT and F-FDG-PET/CT within 72 h of each other, reported by an experienced radiologist and nuclear medicine specialist, respectively in a blinded manner. CECT and PET-CT findings were compared and analyzed. Final diagnosis was based on histology and/or follow-up (ranging from 6 to 12 months). RESULTS: The sensitivity and specificity of CECT in the detection of hepatic metastases was 87.9 and 16.7%, respectively, whereas that of PET/CT was 97 and 75%, respectively. This study showed the superiority of PET/CT over CECT in the detection of hepatic metastases, irrespective of the primary site. This was especially owing to the latter's inability to reliably distinguish small (less than 15 mm) lesions as benign or malignant. CONCLUSION: Many studies have been conducted on the impact of FDG-PET/CT in the evaluation of hepatic metastases, especially from colorectal primary. Very few prospective studies, however, have been conducted on its role in evaluation of hepatic metastases from nongastrointestinal primaries. Despite its superior performance, it cannot replace CECT for this purpose, owing to the low but definite risk of false positivity based on PET-CT findings alone. Inclusion of CECT in PET/CT protocols may enable us to achieve a higher diagnostic accuracy. This suggests the need for a large prospective study with serial evaluations and pathological correlation.
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Medios de Contraste , Fluorodesoxiglucosa F18 , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/secundario , Tomografía de Emisión de Positrones/métodos , Radiografía Abdominal/métodos , Tomografía Computarizada por Rayos X/métodos , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Radiofármacos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Técnica de Sustracción , Adulto JovenRESUMEN
Lung cancer (LC) has an unfavorable prognosis especially when the disease is extensive at presentation. Accurate staging is therefore needed for treatment planning of these patients. In the present study the role of positron emission tomography/computerized tomography (PET/CT) in the detection of extra thoracic metastases in LC is being evaluated. In all 52 of our patients with stage IIIA or lower of LC disease, a whole body (18)F-FDG PET/CT was performed. All patients were also subjected to general clinical evaluation, chest X-rays and chest contrast enhanced CT (CECT) and were confirmed by histopathology or magnetic resonance imaging or radiology. Incidental extra thoracic malignant lesions were found by (18)F-FDG PET/CT in 9 out of the 52 patients (17.3%). No false positive lesions were found. As for the primary LC diagnosed by fine needle aspiration cytology (FNAC): (18)F-FDG PET/CT diagnosed all 52 cases, CECT detected 46 cases and chest X-rays detected 28 cases. The diagnostic accuracy was 100%, 92% and 53.8% respectively. As for the 9 cases with extrathoracic metastases diagnosed by (18)F-FDG PET/CT they were confirmed: by biopsy 6, by MRI 2 and by X-rays with or without biopsy 2. In conclusion, (18)F-FDG PET/CT had better diagnostic accuracy in diagnosing LC stage IIIA or lower, than CECT or chest X-rays. Extrathoracic metastases were high: 9/52 as diagnosed by (18)F-FDG PET/CT and standardized up take value.
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Fluorodesoxiglucosa F18 , Neoplasias Pulmonares/diagnóstico , Tomografía de Emisión de Positrones/métodos , Tomografía Computarizada por Rayos X/métodos , Adulto , Anciano , Femenino , Humanos , Incidencia , Metástasis Linfática , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Radiofármacos , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
A 37-year-old male who underwent a central hepatectomy of the liver for hepatocellular carcinoma (HCC) was referred for an (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) study to rule out tumor recurrence or metastases. The scan showed a recurrent hepatic mass at the operative site, along with low-grade uptake in bilateral pulmonary metastases, mediastinal and hilar lymph nodes, and few skeletal sites. A non-FDG avid intracranial extradural mass was visualized in the right frontal lobe. The (11)C-methionine PET/CT scan performed subsequently revealed a larger area of involvement at the primary site, along with widespread metastases to the lungs, mediastinal, hilar, and abdominal lymph nodes, and multiple skeletal sites. Further, dural metastasis with high tracer uptake was noted in the frontal region. To the best of our knowledge, this is the first case documented in the literature, wherein (11)C-methionine PET/CT played a significant role in delineating the widespread dissemination, including the extremely rare dural involvement in a case of HCC. This report highlights the potential value of (11)C-methionine PET/CT in assessing the hepatic and extrahepatic tumor burden in cases of HCC, especially in clinically unexpected locations.
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Positron emission tomography (PET) imaging with F-18 fluorodeoxyglucose (FDG) can be used as a downstream marker of neuronal injury, a hallmark of neurodegenerative dementias. Characteristic patterns of regional glucose metabolism have been used to classify the dementia subtypes, namely Alzheimer's dementia (AD), frontotemporal dementia (FTD), diffuse Lewy body (DLBD) and vascular dementia (VD). We undertook this study to assess the utility of FDG-PET in the differential diagnosis of dementia subtypes. One hundred and twenty-five patients diagnosed with dementia were referred from cognitive disorders and memory clinics of speciality neurology centres for the FDG-PET study. Imaging-based diagnosis of dementia type was established in 101 patients by visual assessment of individual scans by a PET physician blinded to the clinical diagnosis. The results were compared with an 18-month follow-up clinical assessment made by the specialist neurologist. Concordance of visual evaluation of FDG-PET scans with clinical diagnosis of the dementia type was achieved in 90% of patients scanned. This concordance was 93.4% for AD, 88.8% for FTD, 66.6% for DLBD and 92.3% for the other dementia syndromes. FDG-PET performed after the initial work-up of dementias is useful for supporting the clinical diagnosis of dementia subtype.
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Demencia/diagnóstico por imagen , Demencia/metabolismo , Fluorodesoxiglucosa F18/metabolismo , Enfermedades Neurodegenerativas/diagnóstico por imagen , Tomografía de Emisión de Positrones , Radiofármacos/metabolismo , Anciano , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/metabolismo , Síndrome de Creutzfeldt-Jakob/diagnóstico por imagen , Síndrome de Creutzfeldt-Jakob/metabolismo , Demencia/psicología , Demencia Vascular/diagnóstico por imagen , Demencia Vascular/metabolismo , Diagnóstico Diferencial , Femenino , Demencia Frontotemporal/diagnóstico por imagen , Demencia Frontotemporal/metabolismo , Humanos , Enfermedad por Cuerpos de Lewy/diagnóstico por imagen , Enfermedad por Cuerpos de Lewy/metabolismo , Masculino , Persona de Mediana Edad , Enfermedades Neurodegenerativas/metabolismo , Pruebas Neuropsicológicas , Fenotipo , Tomografía de Emisión de Positrones/métodos , Reproducibilidad de los Resultados , Tomografía Computarizada por Rayos XRESUMEN
OBJECTIVES: The purpose of this study was to evaluate the performance of l-[methyl-()11C]methionine (11C-MET) PET/CT and MRI (with the inclusion of advanced imaging techniques, namely, MR spectroscopy and MR perfusion) in the assessment of tumor recurrence in high-grade gliomas. PATIENTS AND METHODS: Twenty-nine patients with high-grade gliomas who underwent surgical resection, external beam radiation therapy, and standard regimens of chemotherapy were subjected to MRI (conventional, MR perfusion, and MR spectroscopy) and 11C-MET PET/CT scans. A definitive diagnosis was made based on histopathology and/or long-term clinical and radiological follow-up. Several indices were obtained for lesion characterization, namely, SUVmean, SUVmax, and mean lesion-to-normal tissue on PET/CT, as well as relative cerebral blood volume and choline-to-creatine ratio on MRI. RESULTS: Histological examination revealed viable tumor cells in 19 cases, whereas the remaining 10 were deemed to be negative based on histology (3 cases) or long-term follow-up (7 cases). All the quantitative indices mentioned previously tended to be higher in patients with tumor recurrence/residual. The sensitivity, specificity, and accuracy of 11C-MET PET/CT in identifying tumor recurrence/residual were 94.7%, 80%, and 89.6%, respectively, whereas that of MRI were 84.2%, 90%, and 86.2%, respectively. CONCLUSIONS: Both 11C-MET PET/CT and MRI (with the inclusion of advanced MRI techniques) demonstrated a high diagnostic performance in the identification of tumor residual/recurrence in high-grade gliomas posttherapy. Although 11C-MET PET/CT seemed to be more sensitive, whereas advanced MRI seemed more specific, there was no statistically significant difference in the diagnostic performance of either modality in the present study. Further studies with a larger group of patients are warranted.
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Neoplasias Encefálicas/diagnóstico por imagen , Glioma/diagnóstico por imagen , Imagen por Resonancia Magnética , Imagen Multimodal , Recurrencia Local de Neoplasia/diagnóstico por imagen , Tomografía de Emisión de Positrones , Tomografía Computarizada por Rayos X , Adolescente , Adulto , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/terapia , Radioisótopos de Carbono , Femenino , Glioma/patología , Glioma/terapia , Humanos , Masculino , Metionina/análogos & derivados , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , RadiofármacosRESUMEN
BACKGROUND AND OBJECTIVE: People with amnestic mild cognitive impairment (aMCI) are at a higher risk of developing Alzheimers Dementia (AD) than their cognitively normal peers. Decreased glucose metabolism with F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) is a downstream marker of neuronal injury and neurodegeneration. The risk of developing AD is higher in patients with aMCI who have a pattern of AD related glucose metabolic changes on FDG-PET than those who do not have these changes. We evaluated the utility of visual and 'statistical parametric mapping (SPM)-supported reading' of the FDG-PET scans of patients clinically classified as aMCI for identification of predementia patterns and for prediction of their progression to AD (PTAD). PATIENTS AND METHODS: A total of 35 patients diagnosed as aMCI (mini mental state examination (MMSE) score ≥ 25) at the cognitive disorders and memory (CDM) clinic of speciality neurology centers were referred for a resting FDG-PET study. All patients had a detailed neurological, neuropsychological, and magnetic resonance imaging (MRI) evaluation prior to referral. Mean age of patients was 67.9 ± 8.7 (standard deviation (SD)) years, male: female (M: F) =26:9. Twenty healthy age-matched controls were included in the study for SPM (http://www.fil.ion.ucl.ac.uk/spm/). Scans were interpreted visually and using SPM. Each scan was classified as high, intermediate, or low likelihood for PTAD. RESULTS: On visual analysis, four scans were classified as high likelihood of PTAD and reveled hypometabolism in AD related territories. Seven patients had hypometabolism in at least one AD related territory and were classified as intermediate likelihood for PTAD. Two patients had hypometabolism in other than AD territories, while 22 patients did not show any significant hypometabolism on their FDG-PET scans and were classified as low likelihood for PTAD. SPM analysis of these cases confirmed the areas hypometabolism in all 13 patients compared to a normal subgroup (P < 0.05). On follow-up of 24 months, all four cases with high likelihood scans had progression of cognitive deficits and were confirmed as AD in the CDM clinic while none of the others showed cognitive decline. INTERPRETATION AND CONCLUSION: A pattern of AD hypometabolism on the FDG-PET study is useful for predicting PTAD. A longer follow-up of patients with hypometabolism in single AD territories is needed to predict their clinical behavior.
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Malignant peripheral nerve sheath tumors (MPNSTs) are rare tumors, with an estimated incidence of 0.1/100,000/year. They are regarded as a rare variety of soft-tissue sarcomas that derive from peripheral nerves or from cells associated with the nerve sheath. Until 50% of observed MPNSTs occur in patients with neurofibromatosis 1 (NF1). The typical presenting signs and symptoms of a PNST are a palpable mass involving a peripheral nerve, loss of nerve function and/or pain. Recently, positron emission tomography (PET) has been used to detect 18F-fluorodeoxyglucose uptake in these tumors. Most of the PET studies have been reported in patients with NF1. We report a case of sporadic MPNST masquerading as infectious dermatoses, with an unusual PET/computed tomography presentation.
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AIM: The striatal-to-occipital ratio (SOR) is commonly used as an analytical parameter in L-3,4-dihydroxy-6-18F-fluorophenylalanine (FDOPA) PET studies. It has been shown to be useful in differentiating idiopathic Parkinson's disease (IPD) patients from healthy individuals. We assessed the performance of SORs and subregional ratio of striatal-to-occipital ratios (RSORs) in the clinical assessment of nigrostriatal dopaminergic function for differentiating typical IPD from atypical parkinsonian disorders (APD). MATERIALS AND METHODS: A total of 117 patients referred from movement disorder clinics in speciality neurology centres underwent an FDOPA PET study and were kept under follow-up for at least 2 years. Sixty-five patients (43 IPD and 22 APD) completed the 2-year follow-up and were included in the final analysis. Their PET images were spatially normalized to occipital counts and analysed with three striatal subregional regions of interest (caudate, anterior putamen and posterior putamen) and two occipital regions of interest. The RSORs of the caudate and posterior putamen, the caudate and anterior putamen, the caudate and whole putamen and the anterior putamen and posterior putamen were also calculated and compared between the IPD and APD groups using the t-test. RESULTS: The P values for these SORs were found to be insignificant between IPD and APD patients (caudate: 0.1325; anterior putamem: 0.5469; and posterior putamen: 0.9835). However, the RSORs of the caudate and posterior putamen showed significant differences between these two populations of patients. CONCLUSION: The SOR method is already known to be a good diagnostic tool to differentiate between IPD patients and the normal population. SOR, however, fails to distinguish IPD from APD patients, and hence the RSOR of the caudate and posterior putamen can be utilized to differentiate between them.
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Dihidroxifenilalanina/análogos & derivados , Neostriado/metabolismo , Lóbulo Occipital/metabolismo , Enfermedad de Parkinson/diagnóstico , Enfermedad de Parkinson/metabolismo , Diagnóstico Diferencial , Dihidroxifenilalanina/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neostriado/diagnóstico por imagen , Lóbulo Occipital/diagnóstico por imagen , Enfermedad de Parkinson/diagnóstico por imagen , Tomografía de Emisión de PositronesRESUMEN
A 44-year-old apparently healthy woman presented with a 5-month history of intermittent vaginal bleeding. Clinical examination raised the suspicion of cervical neoplasia which was confirmed to be a metastatic adenocarcinoma on subsequent histopathological evaluation. An F-18 FDG PET/CT scan performed soon after revealed increased uptake in the cervix, extending upwards into the endometrial cavity. Additionally, small FDG avid spiculated soft tissue density masses were visualized in bilateral breast parenchyma, which proved to be lobular carcinoma on sonomammography followed by histopathology. Multiple lytic FDG avid skeletal metastases were also noted. Endometrial biopsy showed infiltrative malignant tumor with cytologic features similar to those observed in the breast biopsy specimen. The entire spectrum of findings pointed to a diagnosis of bilateral lobular carcinoma with uterine, cervical, and skeletal metastasis. Metastasis to the uterus and cervix from a breast primary is extremely rare. Most cases have been diagnosed in the follow-up of known cases of breast carcinoma. Our case is unique in that the patient, who had no prior history of breast carcinoma, was suspected to have a breast primary with cervical and uterine metastasis, based on the PET/CT findings.