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1.
Clin Transl Radiat Oncol ; 36: 99-105, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35965663

RESUMO

Background and purpose: Radiotherapy (RT) is an adjuvant treatment option for glioma patients. Side effects include tissue atrophy, which might be a contributing factor to neurocognitive decline after treatment. The goal of this study was to determine potential atrophy of the hippocampus, amygdala, thalamus, putamen, pallidum and caudate nucleus in glioma patients having undergone magnetic resonance imaging (MRI) before and after RT. Materials and methods: Subcortical volumes were measured using T1-weighted MRI from patients before RT (N = 91) and from longitudinal follow-ups acquired in three-monthly intervals (N = 349). The volumes were normalized to the baseline values, while excluding structures touching the clinical target volume (CTV) or abnormal tissue seen on FLAIR imaging. A multivariate linear effects model was used to determine if time after RT and mean RT dose delivered to the corresponding structures were significant predictors of tissue atrophy. Results: The hippocampus, amygdala, thalamus, putamen, and pallidum showed significant atrophy after RT as function of both time after RT and mean RT dose delivered to the corresponding structure. Only the caudate showed no dose or time dependant atrophy. Conversely, the hippocampus was the structure with the highest atrophy rate of 5.2 % after one year and assuming a mean dose of 30 Gy. Conclusion: The hippocampus showed the highest atrophy rates followed by the thalamus and the amygdala. The subcortical structures here found to decrease in volume indicative of radiosensitivity should be the focus of future studies investigating the relationship between neurocognitive decline and RT.

2.
MAGMA ; 35(1): 145-152, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33786695

RESUMO

OBJECTIVE: Brain atrophy has the potential to become a biomarker for severity of radiation-induced side-effects. Particularly brain tumour patients can show great MRI signal changes over time caused by e.g. oedema, tumour progress or necrosis. The goal of this study was to investigate if such changes affect the segmentation accuracy of normal appearing brain and thus influence longitudinal volumetric measurements. MATERIALS AND METHODS: T1-weighted MR images of 52 glioblastoma patients with unilateral tumours acquired before and three months after the end of radio(chemo)therapy were analysed. GM and WM volumes in the contralateral hemisphere were compared between segmenting the whole brain (full) and the contralateral hemisphere only (cl) with SPM and FSL. Relative GM and WM volumes were compared using paired t tests and correlated with the corresponding mean dose in GM and WM, respectively. RESULTS: Mean GM atrophy was significantly higher for full segmentation compared to cl segmentation when using SPM (mean ± std: ΔVGM,full = - 3.1% ± 3.7%, ΔVGM,cl = - 1.6% ± 2.7%; p < 0.001, d = 0.62). GM atrophy was significantly correlated with the mean GM dose with the SPM cl segmentation (r = - 0.4, p = 0.004), FSL full segmentation (r = - 0.4, p = 0.004) and FSL cl segmentation (r = -0.35, p = 0.012) but not with the SPM full segmentation (r = - 0.23, p = 0.1). CONCLUSIONS: For accurate normal tissue volume measurements in brain tumour patients using SPM, abnormal tissue needs to be masked prior to segmentation, however, this is not necessary when using FSL.


Assuntos
Glioblastoma , Substância Branca , Atrofia/patologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Glioblastoma/diagnóstico por imagem , Glioblastoma/terapia , Substância Cinzenta/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética/métodos , Substância Branca/patologia
3.
EJNMMI Res ; 10(1): 142, 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33226505

RESUMO

BACKGROUND: Deriving individual tumor genomic characteristics from patient imaging analysis is desirable. We explore the predictive value of 2-[18F]FDG uptake with regard to the KRAS mutational status of colorectal adenocarcinoma liver metastases (CLM). METHODS: 2-[18F]FDG PET/CT images, surgical pathology and molecular diagnostic reports of 37 patients who underwent PET/CT-guided biopsy of CLM were reviewed under an IRB-approved retrospective research protocol. Sixty CLM in 39 interventional PET scans of the 37 patients were segmented using two different auto-segmentation tools implemented in different commercially available software packages. PET standard uptake values (SUV) were corrected for: (1) partial volume effect (PVE) using cold wall-corrected contrast recovery coefficients derived from phantom spheres with variable diameter and (2) variability of arterial tracer supply and variability of uptake time after injection until start of PET scan derived from the tumor-to-blood standard uptake ratio (SUR) approach. The correlations between the KRAS mutational status and the mean, peak and maximum SUV were investigated using Student's t test, Wilcoxon rank sum test with continuity correction, logistic regression and receiver operation characteristic (ROC) analysis. These correlation analyses were also performed for the ratios of the mean, peak and maximum tumor uptake to the mean blood activity concentration at the time of scan: SURMEAN, SURPEAK and SURMAX, respectively. RESULTS: Fifteen patients harbored KRAS missense mutations (KRAS+), while another 3 harbored KRAS gene amplification. For 31 lesions, the mutational status was derived from the PET/CT-guided biopsy. The Student's t test p values for separating KRAS mutant cases decreased after applying PVE correction to all uptake metrics of each lesion and when applying correction for uptake time variability to the SUR metrics. The observed correlations were strongest when both corrections were applied to SURMAX and when the patients harboring gene amplification were grouped with the wild type: p ≤ 0.001; ROC area under the curve = 0.77 and 0.75 for the two different segmentations, respectively, with a mean specificity of 0.69 and sensitivity of 0.85. CONCLUSION: The correlations observed after applying the described corrections show potential for assigning probabilities for the KRAS missense mutation status in CLM using 2-[18F]FDG PET images.

4.
Mol Imaging Biol ; 17(3): 297-312, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25672749

RESUMO

This paper summarises the proceedings and discussions at the third annual workshop held in Tübingen, Germany, dedicated to the advancement of the technical, scientific and clinical applications of combined PET/MRI systems in humans. Two days of basic scientific and technical instructions with "hands-on" tutorials were followed by 3 days of invited presentations from active researchers in this and associated fields augmented by round-table discussions and dialogue boards with specific themes. These included the use of PET/MRI in paediatric oncology and in adult neurology, oncology and cardiology, the development of multi-parametric analyses, and efforts to standardise PET/MRI examinations to allow pooling of data for evaluating the technology. A poll taken on the final day demonstrated that over 50 % of those present felt that while PET/MRI technology underwent an inevitable slump after its much-anticipated initial launch, it was now entering a period of slow, progressive development, with new key applications emerging. In particular, researchers are focusing on exploiting the complementary nature of the physiological (PET) and biochemical (MRI/MRS) data within the morphological framework (MRI) that these devices can provide. Much of the discussion was summed up on the final day when one speaker commented on the state of PET/MRI: "the real work has just started".


Assuntos
Imageamento por Ressonância Magnética/métodos , Imagem Multimodal/métodos , Tomografia por Emissão de Pósitrons/métodos , Animais , Cardiologia/métodos , Alemanha , Humanos , Processamento de Imagem Assistida por Computador/métodos , Oncologia/métodos , Neurologia/métodos
5.
Phys Med Biol ; 59(11): 2713-26, 2014 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-24800752

RESUMO

The aim of this paper is to describe a new automatic method for compensation of metal-implant-induced segmentation errors in MR-based attenuation maps (MRMaps) and to evaluate the quantitative influence of those artifacts on the reconstructed PET activity concentration. The developed method uses a PET-based delineation of the patient contour to compensate metal-implant-caused signal voids in the MR scan that is segmented for PET attenuation correction. PET emission data of 13 patients with metal implants examined in a Philips Ingenuity PET/MR were reconstructed with the vendor-provided method for attenuation correction (MRMap(orig), PET(orig)) and additionally with a method for attenuation correction (MRMap(cor), PET(cor)) developed by our group. MRMaps produced by both methods were visually inspected for segmentation errors. The segmentation errors in MRMap(orig) were classified into four classes (L1 and L2 artifacts inside the lung and B1 and B2 artifacts inside the remaining body depending on the assigned attenuation coefficients). The average relative SUV differences (ε(rel)(av)) between PET(orig) and PET(cor) of all regions showing wrong attenuation coefficients in MRMap(orig) were calculated. Additionally, relative SUV(mean) differences (ε(rel)) of tracer accumulations in hot focal structures inside or in the vicinity of these regions were evaluated. MRMap(orig) showed erroneous attenuation coefficients inside the regions affected by metal artifacts and inside the patients' lung in all 13 cases. In MRMap(cor), all regions with metal artifacts, except for the sternum, were filled with the soft-tissue attenuation coefficient and the lung was correctly segmented in all patients. MRMap(cor) only showed small residual segmentation errors in eight patients. ε(rel)(av) (mean ± standard deviation) were: (-56 ± 3)% for B1, (-43 ± 4)% for B2, (21 ± 18)% for L1, (120 ± 47)% for L2 regions. ε(rel) (mean ± standard deviation) of hot focal structures were: (-52 ± 12)% in B1, (-45 ± 13)% in B2, (19 ± 19)% in L1, (51 ± 31)% in L2 regions. Consequently, metal-implant-induced artifacts severely disturb MR-based attenuation correction and SUV quantification in PET/MR. The developed algorithm is able to compensate for these artifacts and improves SUV quantification accuracy distinctly.


Assuntos
Artefatos , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Metais , Tomografia por Emissão de Pósitrons/métodos , Próteses e Implantes , Imagem Corporal Total/métodos , Algoritmos , Automação , Humanos , Neoplasias/diagnóstico por imagem
6.
Nuklearmedizin ; 53(3): 67-77, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24553628

RESUMO

UNLABELLED: Quantitative positron emission tomography (PET) requires accurate scanner calibration, which is commonly performed using phantoms. It is not clear to what extent this procedure ensures quantitatively correct results in vivo, since certain conditions differ between phantom and patient scans. AIM: We, therefore, have evaluated the actual quantification accuracy in vivo of PET under clinical routine conditions. PATIENTS, METHODS: We determined the activity concentration in the bladder in patients undergoing routine [18F]FDG whole body investigations with three different PET scanners (Siemens ECAT EXACT HR+ PET: n = 21; Siemens Biograph 16 PET/CT: n = 16; Philips Gemini-TF PET/CT: n = 19). Urine samples were collected immediately after scan. Activity concentration in the samples was determined in well counters cross-calibrated against the respective scanner. The PET (bladder) to well counter (urine sample) activity concentration ratio was determined. RESULTS: Activity concentration in the bladder (PET) was systematically lower than in the urine samples (well counter). The patient-averaged PET to well counter ratios for the investigated scanners are (mean ± SEM): 0.881 ± 0.015 (ECAT HR+), 0.898 ± 0.024 (Biograph 16), 0.932 ± 0.024 (Gemini-TF). These values correspond to underestimates by PET of 11.9%, 10.2%, and 6.8%, respectively. CONCLUSIONS: The investigated PET systems consistently underestimate activity concentration in the bladder. The comparison of urine samples with PET scans of the bladder is a straightforward means for in vivo evaluation of the expectable quantification accuracy. The method might be interesting for multi-center trials, for additional quality assurance in PET and for investigation of PET/MR systems for which clear proof of sufficient quantitative accuracy in vivo is still missing.


Assuntos
Fluordesoxiglucose F18/farmacocinética , Fluordesoxiglucose F18/urina , Imagens de Fantasmas/normas , Tomografia por Emissão de Pósitrons/instrumentação , Tomografia por Emissão de Pósitrons/normas , Radiometria/normas , Bexiga Urinária/metabolismo , Calibragem , Desenho de Equipamento , Análise de Falha de Equipamento/métodos , Análise de Falha de Equipamento/normas , Alemanha , Humanos , Radiometria/instrumentação , Compostos Radiofarmacêuticos/sangue , Compostos Radiofarmacêuticos/farmacocinética , Valores de Referência , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Bexiga Urinária/diagnóstico por imagem
7.
Phys Med Biol ; 59(3): 561-77, 2014 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-24434600

RESUMO

The aim of this study is the evaluation of on-the-fly volume of intersection computation for system's geometry modelling in 3D PET image reconstruction. For this purpose we propose a simple geometrical model in which the cubic image voxels on the given Cartesian grid are approximated with spheres and the rectangular tubes of response (ToRs) are approximated with cylinders. The model was integrated into a fully 3D list-mode PET reconstruction for performance evaluation. In our model the volume of intersection between a voxel and the ToR is only a function of the impact parameter (the distance between voxel centre to ToR axis) but is independent of the relative orientation of voxel and ToR. This substantially reduces the computational complexity of the system matrix calculation. Based on phantom measurements it was determined that adjusting the diameters of the spherical voxel size and the ToR in such a way that the actual voxel and ToR volumes are conserved leads to the best compromise between high spatial resolution, low noise, and suppression of Gibbs artefacts in the reconstructed images. Phantom as well as clinical datasets from two different PET systems (Siemens ECAT HR(+) and Philips Ingenuity-TF PET/MR) were processed using the developed and the respective vendor-provided (line of intersection related) reconstruction algorithms. A comparison of the reconstructed images demonstrated very good performance of the new approach. The evaluation showed the respective vendor-provided reconstruction algorithms to possess 34-41% lower resolution compared to the developed one while exhibiting comparable noise levels. Contrary to explicit point spread function modelling our model has a simple straight-forward implementation and it should be easy to integrate into existing reconstruction software, making it competitive to other existing resolution recovery techniques.


Assuntos
Imageamento Tridimensional/métodos , Tomografia por Emissão de Pósitrons/métodos , Idoso , Algoritmos , Neoplasias Esofágicas/diagnóstico por imagem , Humanos , Masculino , Imagens de Fantasmas
9.
IEEE Trans Med Imaging ; 32(11): 2056-63, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24186268

RESUMO

UNLABELLED: The goal of this article is to quantify the influence of truncation artifacts in the magnetic resonance (MR)-based attenuation map (MRMap) on reconstructed positron emission tomography (PET) image volumes and to propose a new method for minimizing this influence. METHODS: PET data sets of 20 patients investigated in a Philips Ingenuity PET/MR were reconstructed with and without applying two different methods for truncation compensation (TC1 vendor-provided, TC2 newly developed). In this patient group, the extent of truncation artifacts and quality of the truncation compensation (TC) was assessed visually in the MRMaps. In three additional patients MRMaps generated by algorithm TC2 could be compared to the ground truth of transmission-based attenuation maps obtained with a Siemens ECAT HR(+) scanner. The influence of truncation on regional SUVs in lesions, other hot structures (bladder, kidney, myocardium) and the arms was assessed in suitable volume of interests (VOI). RESULTS: Truncation compensated MRMaps exhibited residual artifacts in the arms in 16 patients for algorithm TC1 and to a lesser extent in eight patients for algorithm TC2. Compared to the transmission-based attenuation maps algorithm TC2 slightly overestimated the size of the truncated arms by 0.3 cm in the radial direction. Without truncation compensation, VOIs located in the trunk showed an average SUVmax underestimation of less than 5.4% relative to the results obtained with TC2. Inside the patients' arms underestimations up to 46.5% were found. CONCLUSION: In the trunk, standardized uptake values (SUV) underestimations due to truncation artifacts in the MRMap are rather small. Inside the arms, severe SUV underestimations can occur. Therefore, reliable TC is mandatory and can be achieved by applying the newly developed algorithm TC2 which has yielded promising results so far. Implementation of the proposed method is straightforward and should be easily adaptable to other PET/MR systems.


Assuntos
Artefatos , Imageamento por Ressonância Magnética/métodos , Tomografia por Emissão de Pósitrons/métodos , Imagem Corporal Total/métodos , Humanos , Neoplasias/patologia , Estudos Retrospectivos
10.
Med Phys ; 40(8): 082503, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23927348

RESUMO

PURPOSE: Accurate volumetric tumor delineation is of increasing importance in radiation treatment planning. Many tumors exhibit only moderate tracer uptake heterogeneity and delineation methods using an adaptive threshold lead to robust results. These methods use a tumor reference value R (e.g., ROI maximum) and the tumor background Bg to compute the volume reproducing threshold. This threshold corresponds to an isocontour which defines the tumor boundary. However, the boundaries of strongly heterogeneous tumors can not be described by an isocontour anymore and therefore conventional threshold methods are not suitable for accurate delineation. The aim of this work is the development and validation of a delineation method for heterogeneous tumors. METHODS: The new method (voxel-specific threshold method, VTM) can be considered as an extension of an adaptive threshold method (lesion-specific threshold method, LTM), where instead of a lesion-specific threshold for the whole ROI, a voxel-specific threshold is computed by determining for each voxel Bg and R in the close vicinity of the voxel. The absolute threshold for the considered voxel is then given by Tabs=T×(R-Bg)+Bg, where T=0.39 was determined with phantom measurements. VALIDATION: 30 clinical datasets from patients with non-small-cell lung cancer were used to generate 30 realistic anthropomorphic software phantoms of tumors with different heterogeneities and well-known volumes and boundaries. Volume delineation was performed with VTM and LTM and compared with the known lesion volumes and boundaries. RESULTS: In contrast to LTM, VTM was able to reproduce the true tumor boundaries accurately, independent of the heterogeneity. The deviation of the determined volume from the true volume was (0.8±4.2)% for VTM and (11.0±16.4)% for LTM. CONCLUSIONS: In anthropomorphic software phantoms, the new method leads to promising results and to a clear improvement of volume delineation in comparison to conventional background-corrected thresholding. In the next step, the suitability for clinical routine will be further investigated.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Tomografia por Emissão de Pósitrons/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Carga Tumoral , Algoritmos , Automação , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Neoplasias Pulmonares/radioterapia , Masculino
11.
Ann Hematol ; 92(1): 125-7, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22820970

Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Anaplásico de Células Grandes/tratamento farmacológico , Terapia de Alvo Molecular , Proteínas de Neoplasias/antagonistas & inibidores , Transplante de Células-Tronco de Sangue Periférico , Inibidores de Proteínas Quinases/uso terapêutico , Pirazóis/uso terapêutico , Piridinas/uso terapêutico , Receptores Proteína Tirosina Quinases/antagonistas & inibidores , Adulto , Quinase do Linfoma Anaplásico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Brentuximab Vedotin , Carmustina/administração & dosagem , Cisplatino/administração & dosagem , Terapia Combinada , Ensaios de Uso Compassivo , Crizotinibe , Ciclofosfamida/administração & dosagem , Citarabina/administração & dosagem , Dexametasona/administração & dosagem , Doxorrubicina/administração & dosagem , Etoposídeo/administração & dosagem , Humanos , Imunoconjugados/uso terapêutico , Transfusão de Linfócitos , Linfoma Anaplásico de Células Grandes/complicações , Linfoma Anaplásico de Células Grandes/enzimologia , Linfoma Anaplásico de Células Grandes/cirurgia , Masculino , Melfalan/administração & dosagem , Proteínas de Neoplasias/análise , Prednisona/administração & dosagem , Receptores Proteína Tirosina Quinases/análise , Indução de Remissão , Respiração Artificial , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/terapia , Transplante Homólogo , Vincristina/administração & dosagem
12.
Q J Nucl Med Mol Imaging ; 56(3): 247-67, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22695336

RESUMO

The integration of positron emission tomography (PET) and magnetic resonance imaging (MRI) in a combined PET/MR scanner is attracting much interest. With this new bimodal approach novel functional-anatomical and multiparametric applications become feasible, which can be expected to deliver information beyond that accessible by separately applied modalities. Although the two technologies where initially regarded as inherently incompatible, different solutions have been developed and implemented to realise PET/MR instruments for both small animal and human bimodal imaging. The present review first summarizes the basic options for possible PET/MR designs. A chronological outline describes the evolution from the first ideas, how PET and MR imaging might be combined, over different experimental solutions to the systems recently realized by industry. The BrainPET/MR and the mMR developed by Siemens and the Philips Ingenuity TF PET/MR are characterised and application examples are provided illustrating the features of these instruments. Based on own experiences and those reported in different publications a number of open issues are discussed. Finally a short comparative analysis on the status and perspectives of human PET/MR imaging is given.


Assuntos
Imageamento por Ressonância Magnética/métodos , Tomografia por Emissão de Pósitrons/métodos , Integração de Sistemas , Animais , Encéfalo/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética/instrumentação , Tomografia por Emissão de Pósitrons/instrumentação , Imagem Corporal Total
13.
Nuklearmedizin ; 51(6): 239-43, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22684530

RESUMO

Diagnosis of Alzheimer's disease (AD) with positron emission tomography (PET) using 18F-fluorodeoxyglucose (FDG) relies on typical alterations of brain glucose metabolism which are, however, not disease specific. Amyloid-ß imaging has not entered clinical routine yet. Post mortem histological specimen of brain tissue from AD patients revealed enhanced expression of the chemotactic cytocine receptor 1 (CCR1). PARTICIPANTS, METHODS: CCR1-antagonist ZK811460 was labeled with fluorine-18 to explore its possible use as specific diagnostic tool in AD. Tracer characterization comprising PET imaging of brain and metabolite analysis was performed in AD patients and controls. RESULTS: Neither qualitative evaluation nor quantitative compartment analysis of PET data did show any enhanced binding of the 18F-labeled CCR1-antagonist in the brain of AD patients or controls. CONCLUSION: 18F-ZK811460 did not fulfill the expectation as diagnostic tracer in PET imaging of AD.


Assuntos
Doença de Alzheimer/diagnóstico por imagem , Radioisótopos de Flúor , Compostos de Fenilureia , Piperazinas , Receptores CCR1/antagonistas & inibidores , Idoso , Doença de Alzheimer/metabolismo , Feminino , Radioisótopos de Flúor/química , Humanos , Marcação por Isótopo , Masculino , Compostos de Fenilureia/síntese química , Piperazinas/síntese química , Cintilografia , Compostos Radiofarmacêuticos/síntese química , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
14.
Nuklearmedizin ; 51(1): 9-16, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22027997

RESUMO

AIM: Evaluation of a dedicated software tool for automatic delineation of 3D regions of interest in oncological PET. PATIENTS, METHODS: The applied procedure encompasses segmentation of user-specified subvolumes within the tomographic data set into separate 3D ROIs, automatic background determination, and local adaptive thresholding of the background corrected data. Background correction and adaptive thresholding are combined in an iterative algorithm. Nine experienced observers used this algorithm for automatic delineation of a total of 37 ROIs in 14 patients. Additionally, the observers delineated the same ROIs also manually (using a freely chosen threshold for each ROI) and the results of automatic and manual ROI delineation were compared. RESULTS: For the investigated 37 ROIs the manual delineation shows a strong interobserver variability of (26.8±6.3)% (range: 15% to 45%) while the corresponding value for automatic delineation is (1.1±1.0)% (range: <0.1% to 3.6%). The fractional deviation of the automatic volumes from the observer-averaged manual ones is (3.7±12.7)%. CONCLUSION: The evaluated software provides results in very good agreement with observer-averaged manual evaluations, facilitates and accelerates the volumetric evaluation, eliminates the problem of interobserver variability and appears to be a useful tool for volumetric evaluation of oncological PET in clinical routine.


Assuntos
Algoritmos , Interpretação de Imagem Assistida por Computador/métodos , Imageamento Tridimensional/métodos , Neoplasias/diagnóstico por imagem , Reconhecimento Automatizado de Padrão/métodos , Tomografia por Emissão de Pósitrons/métodos , Adulto , Idoso , Feminino , Humanos , Aumento da Imagem/métodos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
15.
Bioorg Med Chem ; 15(13): 4511-9, 2007 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-17467995

RESUMO

The fluoroalkyl-containing tropane derivative 2beta-carbo-2'-fluoroethoxy-3beta-(4-bromo-phenyl)tropane (MCL-322) is a highly potent and moderately selective ligand for the dopamine transporter (DAT). The compound was labeled with the short-lived positron emitter (18)F in a single step by nucleophilic displacement of the corresponding tosylate precursor MCL-323 with no-carrier-added [(18)F]fluoride. The positron emission tomography (PET) radiotracer 2beta-carbo-2'-[(18)F]fluoroethoxy-3beta-(4-bromo-phenyl)tropane [(18)F]MCL-322 was obtained in decay-corrected radiochemical yields of 30-40% at a specific radioactivity of 1.6-2.4Ci/mumol (60-90GBq/mumol) at the end-of-synthesis (EOS). Small animal PET, ex vivo and in vivo biodistribution experiments in rats demonstrated a high uptake in the striatum (3.2% ID/g) 5min after injection, which increased to 4.2% ID/g after 60min. The uptake in the cerebellum was 1.8% ID/g and 0.6% ID/g after 5min and 60min post-injection, respectively. Specific binding to DAT of [(18)F]MCL-322 was confirmed by blocking experiments using the high affinity DAT ligand GBR 12909. The radiopharmacological characterization was completed with metabolite and autoradiographic studies confirming the selective uptake of [(18)F]MCL-322 in the striatum. It is concluded that the simple single-step radiosynthesis of [(18)F]MCL-322 and the promising radiopharmacological data make [(18)F]MCL-322 an attractive candidate for the further development of a PET radiotracer potentially suitable for clinical DAT imaging in the human brain.


Assuntos
Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Compostos Radiofarmacêuticos/síntese química , Tropanos/síntese química , Animais , Autorradiografia , Ligação Competitiva/efeitos dos fármacos , Biotransformação , Encéfalo/diagnóstico por imagem , Marcação por Isótopo , Imageamento por Ressonância Magnética , Masculino , Piperazinas/farmacologia , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos/farmacocinética , Ratos , Ratos Wistar , Distribuição Tecidual , Tropanos/farmacologia
17.
Amino Acids ; 29(4): 341-53, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16003499

RESUMO

The central distinguishing feature of positron emission tomography (PET) is its ability to investigate quantitatively regional cellular and molecular transport processes in vivo with good spatial resolution. This review wants to provide a concise overview of the established principles underlying quantitative data evaluations of the acquired PET images. Especially, the compartment modelling framework is discussed on which virtually all quantification methods utilized in PET are based. The aim of the review is twofold: first, to provide the reader with an idea of the theoretical framework and mathematical tools and second, to enable an intuitive grasp of the possibilities and limitations of a quantitative approach to PET data evaluation. This should facilitate an understanding of how PET measurements translate into quantities such as regional blood flow, volume of distribution, and metabolic rates of specific substrates.


Assuntos
Modelos Biológicos , Tomografia por Emissão de Pósitrons/métodos , Radioisótopos/farmacocinética , Animais , Compartimentos de Líquidos Corporais , Humanos , Sensibilidade e Especificidade
18.
Amino Acids ; 29(4): 389-404, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16012780

RESUMO

The human organism is exposed to numerous processes that generate reactive oxygen species (ROS). ROS may directly or indirectly cause oxidative modification and damage of proteins. Protein oxidation is regarded as a crucial event in the pathogenesis of various diseases ranging from rheumatoid arthritis to Alzheimer's disease and atherosclerosis. As a representative example, oxidation of low density lipoprotein (LDL) is regarded as a crucial event in atherogenesis. Data concerning the role of circulating oxidized LDL (oxLDL) in the development and outcome of diseases are scarce. One reason for this is the shortage of methods for direct assessment of the metabolic fate of circulating oxLDL in vivo. We present an improved methodology based on the radiolabelling of apoB-100 of native LDL (nLDL) and oxLDL, respectively, with the positron emitter fluorine-18 ((18)F) by conjugation with N-succinimidyl-4-[(18)F]fluorobenzoate ([(18)F]SFB). Radiolabelling of both nLDL and oxLDL using [(18)F]SFB causes neither additional oxidative structural modifications of LDL lipids and proteins nor alteration of their biological activity and functionality, respectively, in vitro. The method was further evaluated with respect to the radiopharmacological properties of both [(18)F]fluorobenzoylated nLDL and oxLDL by biodistribution studies in male Wistar rats. The metabolic fate of [(18)F]fluorobenzoylated nLDL and oxLDL in rats in vivo was further delineated by dynamic positron emission tomography (PET) using a dedicated small animal tomograph (spatial resolution of 2 mm). From this study we conclude that the use of [(18)F]FB-labelled LDL particles is an attractive alternative to, e.g., LDL iodination methods, and is of value to characterize and to discriminate the kinetics and the metabolic fate of nLDL and oxLDL in small animals in vivo.


Assuntos
Lipoproteínas LDL/farmacocinética , Tomografia por Emissão de Pósitrons/métodos , Animais , Benzoatos/química , Benzoatos/farmacocinética , Linhagem Celular , Células Cultivadas , Radioisótopos de Flúor , Humanos , Técnicas In Vitro , Marcação por Isótopo/métodos , Cinética , Lipoproteínas LDL/sangue , Lipoproteínas LDL/química , Masculino , Modelos Animais , Oxirredução , Ratos , Ratos Wistar , Valores de Referência , Sensibilidade e Especificidade , Succinimidas/química , Succinimidas/farmacocinética , Fatores de Tempo
19.
Eur J Nucl Med Mol Imaging ; 30(4): 607-11, 2003 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12589476

RESUMO

Visualisation of primary prostate cancer, its relapse and its metastases is a clinically relevant problem despite the availability of state-of-the-art methods such as CT, MRI, transrectal ultrasound and fluorine-18 fluorodeoxyglucose positron emission tomography ((18)F-FDG PET). The aim of this study was to evaluate the efficacy of carbon-11 acetate and (18)F-FDG PET in the detection of prostate cancer and its metastases. Twenty-five patients were investigated during the follow-up of primary prostate cancer, suspected relapse or metastatic disease using (11)C-acetate PET; 15 of these patients were additionally investigated using (18)F-FDG PET. Fourteen patients were receiving anti-androgen treatment at the time of the investigation. Lesions were detected in 20/24 (83%) patients using (11)C-acetate PET and in 10/15 (75%) patients using (18)F-FDG PET. Based on the results of both PET scans, one patient was diagnosed with recurrent lung cancer. Median (18)F-FDG uptake exceeded that of (11)C-acetate in distant metastases (SUV =3.2 vs 2.3). However, in local recurrence and in regional lymph node metastases, (11)C-acetate uptake (median SUVs =2.9 and 3.8, respectively) was higher than that of (18)F-FDG (median SUVs =1.0 and 1.1, respectively). A positive correlation was observed between serum PSA level and both (11)C-acetate uptake and (18)F-FDG uptake. (11)C-acetate seems more useful than (18)F-FDG in the detection of local recurrences and regional lymph node metastases. (18)F-FDG, however, appears to be more accurate in visualising distant metastases. There may be a role for combined (11)C-acetate/(18)F-FDG PET in the follow-up of patients with prostate cancer and persisting or increasing PSA.


Assuntos
Acetatos , Carbono , Fluordesoxiglucose F18 , Recidiva Local de Neoplasia/diagnóstico por imagem , Neoplasias da Próstata/diagnóstico por imagem , Tomografia Computadorizada de Emissão/métodos , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/sangue , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/secundário , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/sangue , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Compostos Radiofarmacêuticos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
20.
Nuklearmedizin ; 42(1): 25-30, 2003 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-12601451

RESUMO

UNLABELLED: In a pilot trial we investigated whether significant differences in prostate cancer (PCA) imaging would be observed using [(11)C]acetate and [(11)C]choline positron emission tomography (PET). METHODS: Twelve patients were studied with both radiotracers. Whole body PET without attenuation correction was performed after injection of 0.95 +/- 0.15 GBq [(11)C]acetate and 0.84 +/- 0.13 GBq [(11)C]choline, respectively, from 5 to 60 min p. i. Focally increased uptake in bone, below the urinary bladder or in a lymph node region was considered as tumour. Primary tumour, lymph node involvement, bone metastases, local recurrence; and no evidence of disease were known in 2, 4, 2, 2; and 2 patients, respectively. RESULTS: [(11)C]Acetate uptake was highest in spleen and pancreas while [(11)C]choline uptake was predominant in liver and kidney parenchyma. However, interindividual variation was high. The potential of both radiotracers to detect known bone lesions, lymph node metastases, and imaging of the primary tumour was identical. However, both failed to detect a small local recurrence in two patients as well as to demonstrate lymph node involvement in one patient, which was confirmed by surgery. CONCLUSIONS: In this preliminary study, uptake of both radiotracers in prostate cancer or its metastases was nearly identical and none of them should be favoured. At present, both radiotracers influence patient management by detection of local recurrence, lymph node, or bone metastases of PCA.


Assuntos
Acetatos/metabolismo , Radioisótopos de Carbono/farmacocinética , Colina/metabolismo , Metástase Neoplásica/diagnóstico por imagem , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Idoso , Idoso de 80 Anos ou mais , Transporte Biológico , Biópsia , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Distribuição Tecidual , Tomografia Computadorizada de Emissão/métodos , Ultrassonografia
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