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1.
Acta Neurochir (Wien) ; 166(1): 139, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38488893

RESUMO

Neurovascular compression of the rostral ventrolateral medulla (RVLM) has been described as a possible cause of refractory essential hypertension. We present the case of a patient affected by episodes of severe paroxysmal hypertension, some episodes associated with vago-glossopharyngeal neuralgia. Classical secondary forms of hypertension were excluded. Imaging revealed a neurovascular conflict between the posterior inferior cerebellar artery (PICA) and the ventrolateral medulla at the level of the root entry zone of the ninth and tenth cranial nerves (CN IX-X REZ). A MVD of a conflict between the PICA and the RVLM and adjacent CN IX-X REZ was performed, resulting in reduction of the frequency and severity of the episodes. Brain MRI should be performed in cases of paroxysmal hypertension. MVD can be considered in selected patients.


Assuntos
Doenças do Nervo Glossofaríngeo , Hipertensão , Humanos , Bulbo/diagnóstico por imagem , Hipertensão/complicações , Nervo Vago , Pressão
2.
AJNR Am J Neuroradiol ; 44(6): 687-692, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37230542

RESUMO

BACKGROUND AND PURPOSE: Endovascular treatment of acute ischemic stroke is now performed more frequently in the late window in radiologically selected patients. However, little is known about whether the frequency and clinical impact of incomplete recanalization and postprocedural cerebrovascular complications differ between early and late windows in the real world. MATERIALS AND METHODS: We retrospectively reviewed all patients with acute ischemic stroke receiving endovascular treatment within 24 hours from 2015 to 2019 and included in the Acute STroke Registry and Analysis of Lausanne. We compared rates of incomplete recanalization and postprocedural cerebrovascular complications (parenchymal hematoma, ischemic mass effect, and 24-hour re-occlusion) in the early (<6 hours) versus late window (6-24 hours, including patients with unknown onset) populations and correlated them with the 3-month clinical outcome. RESULTS: Among 701 patients with acute ischemic stroke receiving endovascular treatment, 29.2% had late endovascular treatment. Overall, incomplete recanalization occurred in 56 patients (8%), and 126 patients (18%) had at least 1 postprocedural cerebrovascular complication. The frequency of incomplete recanalization was similar in early and late endovascular treatment (7.5% versus 9.3%, adjusted P =.66), as was the occurrence of any postprocedural cerebrovascular complication (16.9% versus 20.5%, adjusted P = .36). When analyzing single postprocedural cerebrovascular complications, rates of parenchymal hematoma and ischemic mass effect were similar (adjusted P = .71, adjusted P = .79, respectively), but 24-hour re-occlusion seemed somewhat more frequent in late endovascular treatment (4% versus 8.3%, unadjusted P = .02, adjusted P = .40). The adjusted 3-month clinical outcome in patients with incomplete recanalization or postprocedural cerebrovascular complications was comparable between early and late groups (adjusted P = .67, adjusted P = .23, respectively). CONCLUSIONS: The frequency of incomplete recanalization and of cerebrovascular complications occurring after endovascular treatment is similar in early and well-selected late patients receiving endovascular treatment. Our results demonstrate the technical success and safety of endovascular treatment in well-selected late patients with acute ischemic stroke.


Assuntos
Isquemia Encefálica , Procedimentos Endovasculares , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/epidemiologia , Isquemia Encefálica/terapia , Estudos de Coortes , Estudos Retrospectivos , AVC Isquêmico/etiologia , Resultado do Tratamento , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/métodos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Trombectomia/métodos
3.
AJNR Am J Neuroradiol ; 43(12): 1743-1748, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36423955

RESUMO

BACKGROUND AND PURPOSE: Procedural complications occur in 4%-29% of endovascular treatments in acute ischemic stroke. However, little is known about their predictors and clinical impact in the real world. We aimed to investigate the frequency and clinical impact of procedural complications of endovascular treatment and identify associated risk factors. MATERIALS AND METHODS: From 2015-2019, we retrospectively reviewed all patients with acute ischemic stroke receiving endovascular treatment within 24 hours included in the Acute STroke Registry and Analysis of Lausanne. We identified patients having an endovascular treatment procedural complication (local access complication, arterial perforation, dissection or vasospasm, and embolization in a previously nonischemic territory) and performed logistic regression analyses to identify associated predictors. We also correlated procedural complications with long-term clinical outcome. RESULTS: Of the 684 consecutive patients receiving endovascular treatment, 113 (16.5%) had at least 1 procedural complication. The most powerful predictors were groin puncture off-hours (OR = 2.24), treatment of 2 arterial sites (OR = 2.71), and active smoking (OR = 1.93). Patients with a complication had a significantly less favorable short-term clinical outcome (Δ-NIHSS score of -2.2 versus -4.33, P-value adjusted < .001), but a similar long-term clinical outcome (mRS at 3 months = 3 versus 2, P-value adjusted = .272). CONCLUSIONS: Procedural complications are quite common in endovascular treatment and lead to a less favorable short-term but similar long-term outcome. Their association with treatment off-hours and at 2 arterial sites requires particular attention in these situations to optimize the overall benefit of endovascular treatment.


Assuntos
Isquemia Encefálica , Procedimentos Endovasculares , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , AVC Isquêmico/etiologia , Estudos de Coortes , Estudos Retrospectivos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/tratamento farmacológico , Procedimentos Endovasculares/efeitos adversos , Resultado do Tratamento , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/etiologia , Isquemia Encefálica/terapia , Trombectomia
5.
AJNR Am J Neuroradiol ; 42(3): 422-428, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33509915

RESUMO

BACKGROUND AND PURPOSE: Both ASPECTS and core volume on CTP are used to estimate infarct volume in acute ischemic stroke. To evaluate the potential role of ASPECTS for acute endovascular treatment decisions, we studied the correlation between ASPECTS and CTP core, depending on the timing and the presence of large-vessel occlusion. MATERIALS AND METHODS: We retrospectively reviewed all MCA acute ischemic strokes with standardized reconstructions of CTP maps entered in the Acute STroke Registry and Analysis of Lausanne (ASTRAL) registry. Correlation between ASPECTS and CTP core was determined for early (<6 hours) versus late (6-24 hours) times from stroke onset and in the presence versus absence of large-vessel occlusion. We used correlation coefficients and adjusted multiple linear regression models. RESULTS: We included 1046 patients with a median age of 71.4 years (interquartile range, IQR = 59.8-79.4 years), an NIHSS score of 12 (IQR, 6-18), an ASPECTS of 9 (IQR, 7-10), and a CTP core of 13.6 mL (IQR, 0.6-52.8 mL). The overall correlation between ASPECTS and CTP core was moderate (ρ = -0.49, P < .01) but significantly stronger in the late-versus-early window (ρ = -0.56 and ρ = -0.48, respectively; P = .05) and in the presence versus absence of large-vessel occlusion (ρ = -0.40 and ρ = -0.20, respectively; P < .01). In the regression model, the independent association between ASPECTS and CTP core was confirmed and was twice as strong in late-arriving patients with large-vessel occlusion (ß = -0.21 per 10 mL; 95% CI, -0.27 to -0.15; P < .01) than in the overall population (ß = -0.10; 95% CI, -0.14 to -0.07; P < .01). CONCLUSIONS: In a large cohort of patients with acute ischemic stroke, we found a moderate correlation between ASPECTS and CTP core. However, this was stronger in patients with large-vessel occlusion and longer delay from stroke onset. Our results could support the use of ASPECTS as a surrogate marker of CTP core in late-arriving patients with acute ischemic stroke with large-vessel occlusion.


Assuntos
AVC Isquêmico/diagnóstico por imagem , Imagem de Perfusão/métodos , Tomografia Computadorizada por Raios X/métodos , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , AVC Isquêmico/patologia , Masculino , Pessoa de Meia-Idade , Neuroimagem/métodos , Estudos Retrospectivos , Tempo para o Tratamento
6.
AJNR Am J Neuroradiol ; 40(3): 483-489, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30792249

RESUMO

BACKGROUND AND PURPOSE: Perfusion CT may improve the diagnostic performance of noncontrast CT in acute ischemic stroke. We assessed predictors of focal hypoperfusion in acute ischemic stroke and perfusion CT performance in predicting infarction on follow-up imaging. MATERIALS AND METHODS: Patients from the Acute STroke Registry and Analysis of Lausanne data base with acute ischemic stroke and perfusion CT were included. Clinical and radiologic data were collected. We identified predictors of focal hypoperfusion using multivariate analyses. RESULTS: From the 2216 patients with perfusion CT, 38.2% had an acute ischemic lesion on NCCT and 73.3% had focal hypoperfusion on perfusion CT. After we analyzed 104 covariates, high-admission NIHSS, visual field defect, aphasia, hemineglect, sensory deficits, and impaired consciousness were positively associated with focal hypoperfusion. Negative associations were pure posterior circulation, lacunar strokes, and anticoagulation. After integrating radiologic variables into the multivariate analyses, we found that visual field defect, sensory deficits, hemineglect, early ischemic changes on NCCT, anterior circulation, cardioembolic etiology, and arterial occlusion were positively associated with focal hypoperfusion, whereas increasing onset-to-CT delay, chronic vascular lesions, and lacunar etiology showed negative association. Sensitivity, specificity, and positive and negative predictive values of focal hypoperfusion on perfusion CT for infarct detection on follow-up MR imaging were 66.5%, 79.4%, 96.2%, and 22.8%, respectively, with an overall accuracy of 76.8%. CONCLUSIONS: Compared with NCCT, perfusion CT doubles the sensitivity in detecting acute ischemic stroke. Focal hypoperfusion is independently predicted by stroke severity, cortical clinical deficits, nonlacunar supratentorial strokes, and shorter onset-to-imaging delays. A high proportion of patients with focal hypoperfusion developed infarction on subsequent imaging, as did some patients without focal hypoperfusion, indicating the complementarity of perfusion CT and MR imaging in acute ischemic stroke.


Assuntos
Neuroimagem/métodos , Imagem de Perfusão/métodos , Acidente Vascular Cerebral/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/diagnóstico por imagem , Feminino , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade
7.
J Neurol ; 265(12): 2972-2979, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30327930

RESUMO

INTRODUCTION: PCT is used in the diagnosis of acute neurological syndromes, particularly stroke. We aimed to evaluate PCT abnormalities in patients with acute epileptic seizures or status epilepticus (SE). METHODS: We collected patients undergoing acute PCT for the suspicion of acute ischemic stroke (AIS), who received a final diagnosis of focal seizures or generalised seizures with a post-ictal deficit, with or without concomitant AIS. PCTs were retrospectively analysed for the presence of hyper- and hypoperfusion, and results correlated with delay from seizure onset, aetiology, type of seizures and the presence of electrical SE. RESULTS: Half of the 43 consecutively identified patients had regional PCT abnormalities-hyperperfusion in 13 (30%) and hypoperfusion in 8 (19%)-and 4 (9%) had AIS. Among patients with hyperperfusion, six (46%) had a focal deficit during imaging acquisition (two a normal clinical status, one altered consciousness and four ongoing seizure); nine (69%) of these patients had a SE; none had a stroke. All patients with hypoperfusion had focal neurological deficit; three (37%) of them a simultaneous ischemic stroke (in the remaining five, hypoperfusion was considered to be related to the seizure post-ictal phase). In the 22 with normal perfusion, 9 had a focal deficit (10 a normal clinical status, 2 altered consciousness and 1 ongoing seizure); 3 had a SE, and 1 had a stroke. Patients with SE featured a higher prevalence of hyperperfusion (9/13 [69%] vs. 4/30 [13%] without SE, p = 0.00). CONCLUSION: In patients with acute epileptic seizures, regional hyperperfusion on PCT may suggest an ongoing or recently resolved SE, whereas hypoperfusion may be due to post-ictal state or simultaneous AIS. These observations might help attributing focal deficits to epileptic seizures rather than stroke, allowing for targeted therapy.


Assuntos
Encéfalo/diagnóstico por imagem , Circulação Cerebrovascular , Epilepsia/diagnóstico por imagem , Convulsões/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adulto , Idoso , Idoso de 80 Anos ou mais , Encéfalo/irrigação sanguínea , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/terapia , Epilepsia/fisiopatologia , Epilepsia/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Convulsões/fisiopatologia , Convulsões/terapia , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/terapia , Tomografia Computadorizada por Raios X/métodos
8.
Eur J Neurol ; 25(5): 725-731, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29350878

RESUMO

BACKGROUND AND PURPOSE: The aim was to determine the predictors of focal hypoperfusion on computed tomography (CT) perfusion (CTP) in patients with acute posterior circulation stroke and its association with long-term outcome. METHODS: Patients with posterior circulation stroke were selected from the Acute Stroke Registry and Analysis of Lausanne (ASTRAL) who underwent CTP within 24 h of stroke onset as part of the stroke imaging protocol. Hypoperfusion was defined as an area of visually well demarcated mean transit time prolongation corresponding to an arterial territory on standard reconstruction CTP imaging maps. Areas of hypoperfusion were assessed with the posterior circulation Acute Stroke Prognosis Early CT Score. Clinical and imaging associations with focal hypoperfusion were identified using multiple imputation analyses, and the adjusted functional outcome measured by the modified Rankin Scale at 3 and 12 months was determined. RESULTS: Of the 3595 consecutive patients from the ASTRAL registry between 2003 and 2014, 1070 (29.7%) had a posterior circulation stroke and 436 of these (40.7%) patients had a good quality baseline CTP. 23.1% had early ischaemic changes and 37.4% had focal hypoperfusion. In multiple imputation analysis, visual field deficits, reduced level of consciousness, cardiac and multiple stroke mechanisms, significant vessel pathology and ischaemic changes visible on plain CT were associated with focal hypoperfusion. Focal hypoperfusion was independently associated with outcome at 12 months (odds ratio 2.04, 95% confidence interval 1.22-3.42, P < 0.01). CONCLUSIONS: In posterior circulation stroke patients undergoing acute CTP, multiple clinical, aetiological and radiological variables were associated with focal hypoperfusion. Patients with focal hypoperfusion had a worse 12-month outcome.


Assuntos
Circulação Cerebrovascular/fisiologia , Imagem de Perfusão/métodos , Acidente Vascular Cerebral/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Sistema de Registros , Índice de Gravidade de Doença
9.
Diagn Interv Imaging ; 97(10): 973-989, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27687833

RESUMO

Lung cancer, the most frequent cancer worldwide, is the fourth most frequent cancer in France, with an overall 5-year survival rate of about 15%, directly correlated to the stage of disease at the time of diagnosis and its treatment. The objective of this article is to describe the role, contributions and pitfalls of computed tomography (CT) in clinical TNM staging, primarily to identify patients eligible for curative surgery. TNM staging criteria, last updated in 2009, are discussed along with the new proposals for the 8th edition to be published late 2016. The most crucial CT features for pre-therapy assessment are highlighted.


Assuntos
Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/terapia , Tomografia Computadorizada por Raios X/métodos , Endossonografia/métodos , Humanos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Metástase Linfática/patologia , Mediastinoscopia/métodos , Tomografia Computadorizada Multidetectores/métodos , Estadiamento de Neoplasias/classificação , Estadiamento de Neoplasias/métodos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Sensibilidade e Especificidade , Taxa de Sobrevida , Toracoscopia/métodos
10.
AJNR Am J Neuroradiol ; 37(12): 2310-2316, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27418471

RESUMO

BACKGROUND AND PURPOSE: Patients with vascular parkinsonism have higher cognitive decline and more basal ganglia lesions. We aimed to evaluate the relationship of cognitive impairment with functional connectivity between the basal ganglia and cingulate cortex in vascular parkinsonism. MATERIALS AND METHODS: Thirty patients (8 with vascular parkinsonism and 22 with Parkinson disease) and 23 controls were enrolled. The Mattis Dementia Rating Scale and the Stroop Task were used to assess cognitive decline. MR imaging examinations included T1-MPRAGE, FLAIR, and resting-state fMRI sequences. MPRAGE was segmented to obtain basal ganglia and cingulate cortex volumes. FLAIR was segmented to obtain white matter hyperintensity lesion volume. Resting-state fMRI sequences were used to compare basal ganglia functional connectivity with the cingulate cortex between patients and controls. RESULTS: Patients with vascular parkinsonism exhibited impaired attention, resistance to interference, and inhibitory control and an increased number of errors on the Stroop Task. They also had higher caudate nucleus and white matter hyperintensity lesion volumes, which were positively correlated (ρ = 0.75, P < .0001). Caudate nucleus functional connectivity with the perigenual anterior cingulate cortex was increased in patients with vascular parkinsonism compared with controls and patients with Parkinson disease, and it was positively correlated with the caudate nucleus volume (ρ = 0.44, P = .016). Caudate nucleus functional connectivity with the posterior cingulate cortex was decreased in patients with vascular parkinsonism compared with controls and negatively correlated with the number of errors on the Stroop test (ρ = -0.51, P = .0003). CONCLUSIONS: In patients with vascular parkinsonism, cognitive decline could be related to changes of caudate nucleus functional connectivity with the cingulate cortex at resting-state, which may be induced by ischemia-related remodelling.


Assuntos
Gânglios da Base/fisiopatologia , Encéfalo/fisiopatologia , Disfunção Cognitiva/fisiopatologia , Vias Neurais/fisiopatologia , Doença de Parkinson Secundária/fisiopatologia , Gânglios da Base/patologia , Encéfalo/patologia , Disfunção Cognitiva/etiologia , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Vias Neurais/patologia , Doença de Parkinson Secundária/complicações , Doença de Parkinson Secundária/patologia
11.
Nuklearmedizin ; 53(4): 155-61, 2014 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-24737132

RESUMO

AIM: MRI and PET with 18F-fluoro-ethyl-tyrosine (FET) have been increasingly used to evaluate patients with gliomas. Our purpose was to assess the additive value of MR spectroscopy (MRS), diffusion imaging and dynamic FET-PET for glioma grading. PATIENTS, METHODS: 38 patients (42 ± 15 aged, F/M: 0.46) with untreated histologically proven brain gliomas were included. All underwent conventional MRI, MRS, diffusion sequences, and FET-PET within 3±4 weeks. Performances of tumour FET time-activity-curve, early-to-middle SUVmax ratio, choline / creatine ratio and ADC histogram distribution pattern for gliomas grading were assessed, as compared to histology. Combination of these parameters and respective odds were also evaluated. RESULTS: Tumour time-activity-curve reached the best accuracy (67%) when taken alone to distinguish between low and high-grade gliomas, followed by ADC histogram analysis (65%). Combination of time-activity-curve and ADC histogram analysis improved the sensitivity from 67% to 86% and the specificity from 63-67% to 100% (p < 0.008). On multivariate logistic regression analysis, negative slope of the tumour FET time-activity-curve however remains the best predictor of high-grade glioma (odds 7.6, SE 6.8, p = 0.022). CONCLUSION: Combination of dynamic FET-PET and diffusion MRI reached good performance for gliomas grading. The use of FET-PET/MR may be highly relevant in the initial assessment of primary brain tumours.


Assuntos
Neoplasias Encefálicas/patologia , Glioma/patologia , Imageamento por Ressonância Magnética/métodos , Imagem Multimodal/métodos , Tomografia por Emissão de Pósitrons/métodos , Tirosina/análogos & derivados , Adulto , Feminino , Humanos , Aumento da Imagem/métodos , Masculino , Gradação de Tumores , Variações Dependentes do Observador , Compostos Radiofarmacêuticos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
12.
Cancer Radiother ; 16(2): 152-63, 2012 Apr.
Artigo em Francês | MEDLINE | ID: mdl-22424889

RESUMO

The implementation of new techniques of imaging in the daily practice of the radiation oncologist is a major advance in these last 10 years. This allows optimizing the therapeutic intervals and locoregional control of the disease while limiting side effects. Among them, positron emission tomography (PET) offers an opportunity to the clinician to obtain data relative to the tumoral biological mechanisms, while benefiting from the morphological images of the computed tomography (CT) scan. Recently hybrid PET/CT has been developed and numerous studies aimed at optimizing its use in the planning, the evaluation of the treatment response and the prognostic value. The choice of the radiotracer (according to the type of cancer and to the studied biological mechanism) and the various methods of tumoral delineation, require a regular update to optimize the practices. We propose throughout this article, an exhaustive review of the published researches (and in process of publication) until December 2011, as user guide of PET/CT in all the aspects of the modern radiotherapy (from the diagnosis to the follow-up): biopsy guiding, optimization of treatment planning and dosimetry, evaluation of tumor response and prognostic value, follow-up and early detection of recurrence versus tumoral necrosis. In a didactic purpose, each of these aspects is approached by primary tumoral location, and illustrated with representative iconographic examples. The current contribution of PET/CT and its perspectives of development are described to offer to the radiation oncologist a clear and up to date reading in this expanding domain.


Assuntos
Imagem Multimodal , Neoplasias/diagnóstico por imagem , Neoplasias/radioterapia , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , Feminino , Neoplasias Gastrointestinais/diagnóstico por imagem , Neoplasias Gastrointestinais/radioterapia , Neoplasias dos Genitais Femininos/diagnóstico por imagem , Neoplasias dos Genitais Femininos/radioterapia , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/radioterapia , Linfoma/diagnóstico por imagem , Linfoma/radioterapia , Masculino , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/radioterapia
13.
Nuklearmedizin ; 50(6): 225-33, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21989840

RESUMO

AIM: To visualize neovasculature and/or tumour integrin αvß3 we selected the binding moiety Arg-Gly-Asp-D-Tyr-Lys (RGDyK) coupled to NODAGA for labeling with 68Ga. METHODS: NODAGA-RGDyK (ABX) was labeled with the 68Ga eluate from the 68Ge generator IGG100 using the processor unit PharmTracer. Biodistribution was measured in female Hsd mice sacrificed 10, 30, 60 and 90 min after i.v. injection of 68Ga-NODAGA-RGDyK for OLINDA dosimetry extrapolated to humans. Tumour targeting was studied in SCID mice bearing A431 and other tumour transplants using microPET and biodistribution measurements. RESULTS: Effective half-life of 68Ga-NODAGA-RGDyK was ~25 min for total body and most organs except liver and spleen that showed stable activity retention. With a bladder voiding interval of 0.5 h the calculated effective dose (ED) was 0.012 and 0.016 mSv/MBq for males and females, respectively. Rapid uptake within 10 min was observed in A431 tumours with dynamic PET followed by a slow release. Biodistribution measurements showed a 68Ga-NODAGA-RGDyK uptake in A431 tumours of 3.4±0.4 and 2.7±0.3%ID/g at 1 and 2 h, respectively. Similar uptakes were observed in a mouse and human breast and ovarian cancer xenografts. Co-injection of excess (5 mg/kg) unlabeled NODAGA-RGDyK with the radiotracer reduced tumour uptake at one hour to 0.23±0.01%ID/g, but similarly decreased uptake in normal organs as well. When unlabeled peptide was injected 15 min after 68Ga-NODAGA-RGDyK, uptake diminished particularly in tumour and adrenals, suggestive of a different binding mode compared with other normal tissues. CONCLUSION: NODAGA-RGDyK was reliably labeled with 68Ga and revealed a predicted ED of 0.014 mSv/MBq. Tumour uptake was rapid and significant and was chased with unlabeled RGDyK in a similar manner as adrenal uptake.


Assuntos
Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/metabolismo , Integrina alfaVbeta3/metabolismo , Oligopeptídeos/farmacocinética , Tomografia por Emissão de Pósitrons/métodos , Animais , Carga Corporal (Radioterapia) , Linhagem Celular Tumoral , Avaliação Pré-Clínica de Medicamentos , Feminino , Radioisótopos de Gálio , Compostos Heterocíclicos/química , Compostos Heterocíclicos/farmacocinética , Compostos Heterocíclicos com 1 Anel , Humanos , Integrina alfaVbeta3/química , Taxa de Depuração Metabólica , Camundongos , Camundongos Endogâmicos ICR , Especificidade de Órgãos , Compostos Radiofarmacêuticos/síntese química , Compostos Radiofarmacêuticos/farmacocinética , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Contagem Corporal Total
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