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AIM: [11C]Choline-positron emission tomography in combination with computer tomography ([11C]Choline-PET/CT) is a promising imaging approach for localizing relapsing prostate cancer. We therefore studied performance of [11C]Choline-PET/CT in patients relapsing from prostate cancer after radical prostatectomy (RP) and scheduled for salvage radiation therapy (SRT) in terms of relapse localization and relationship to outcome after SRT. METHODS: In a prospective pilot study we examined 27 patients with [11C]Coline-PET/CT before SRT. All patients had biochemical relapse after RP and were treated with SRT. [11C]Choline-PET/CT was done within 14 days before SRT. RESULTS: Eleven of 27 patients had at follow up of 76.5±5.7 months a favorable long-term response to SRT and needed no specific further prostate cancer related treatment. In 16/27 patients, rising serum PSA concentrations were observed 34.2±20.1 months after SRT, qualifying them as treatment failures. Tumor stage, risk profile and PSA before SRT were not different in long term responders and failures. [11C]Choline-PET/CT showed local relapse in about 50% of both long-term responders failures, locoregional nodal relapse in 4/16 failures and a singular bone metastasis in 1/16 failures. CONCLUSION: [11C]Choline-PET/CT showed in roughly 50% of patients evidence of local relapse within the prostatic fossa. Roughly 30% of treatment failures had evidence of locoregional nodal or distant metastatic disease outside the radiation ports possibly related to treatment failures after SRT. Kaplan-Meier analysis suggested that [11C]Choline-PET/CT positive patients do worse at follow-up in terms of freedom from biochemical recurrence.
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Radioisótopos de Carbono , Colina , Imagen Multimodal , Recurrencia Local de Neoplasia/diagnóstico por imagen , Recurrencia Local de Neoplasia/radioterapia , Tomografía de Emisión de Positrones , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/radioterapia , Radiofármacos , Terapia Recuperativa , Tomografía Computarizada por Rayos X , Anciano , Anciano de 80 o más Años , Humanos , Masculino , Persona de Mediana Edad , PronósticoRESUMEN
PURPOSE: We evaluated the impact of salvage lymph node dissection with adjuvant radiotherapy in patients with nodal recurrence of prostate cancer. By default, nodal recurrence of prostate cancer is treated with palliative antihormonal therapy, which causes serious side effects and invariably leads to the development of hormone refractory disease. MATERIALS AND METHODS: A total of 47 patients with nodal recurrence of prostate cancer based on evidence of (11)C-choline/(18)F-choline ((18)F-fluorethylcholine) positron emission tomography-computerized tomography underwent primary (2 of 52), secondary (45 of 52), tertiary (4 of 52) and quaternary (1 of 52) salvage lymph node dissection with histological confirmation. Of 52 salvage lymph node dissections 27 were followed by radiotherapy. Biochemical response was defined as a prostate specific antigen less than 0.2 ng/ml after salvage therapy. The Kaplan-Meier method, binary logistic regression and Cox regression were used to analyze survival as well as predictors of biochemical response and clinical progression. RESULTS: Mean prostate specific antigen at salvage lymph node dissection was 11.1 ng/ml. A mean of 23.3 lymph nodes were removed per salvage lymph node dissection. Median followup was 35.5 months. Of 52 salvage lymph node dissections 24 resulted in complete biochemical response followed by 1-year biochemical recurrence-free survival of 71.8%. Gleason 6 or less (OR 7.58, p = 0.026), Gleason 7a/b (OR 5.91, p = 0.042) and N0 status at primary therapy (OR 8.01, p = 0.011) were identified as independent predictors of biochemical response. Gleason 8-10 (HR 3.5, p = 0.039) as a preoperative variable, retroperitoneal positive lymph nodes (HR 3.76, p = 0.021) and incomplete biochemical response (HR 4.0, p = 0.031) were identified as postoperative predictors of clinical progression. Clinical progression-free survival was 25.6% and cancer specific survival was 77.7% at 5 years. CONCLUSIONS: Based on (11)C/(18)F-choline positron emission tomography-computerized tomography as a diagnostic tool, salvage lymph node dissection is feasible for the treatment of nodal recurrence of prostate cancer. Most patients experience biochemical recurrence after salvage lymph node dissection. However, a specific population has a lasting complete prostate specific antigen response.
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Escisión del Ganglio Linfático , Recurrencia Local de Neoplasia/radioterapia , Recurrencia Local de Neoplasia/cirugía , Neoplasias de la Próstata/radioterapia , Neoplasias de la Próstata/cirugía , Anciano , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/sangre , Radioterapia Adyuvante , Terapia RecuperativaRESUMEN
Fluorodeoxyglucose-positron emission tomography (FDG-PET)/computed tomography (CT) is able to localize persistent or recurrent disease in differentiated thyroid carcinoma (DTC). The aim of the study was to correlate PET/CT results with precise intraoperative localization of persistent or recurrent papillary and follicular thyroid carcinoma. Patients with differentiated thyroid carcinoma who received FDG-PET scans were prospectively documented. The PET/CT results were correlated with other localization studies (neck ultrasound, ¹³¹I whole-body scan) and accurately compared to intraoperative findings and histopathological examinations. FDG-PET/CT scans were performed in 18 patients, between 16 and 84 years of age, from December 2008 to June 2011. Fourteen patients had papillary thyroid carcinomas and 4 had follicular thyroid carcinomas. All patients had a previous thyroidectomy and radioiodine ablation. Before cervical re-exploration, FDG-PET/CT-positive findings were reported in 14 individuals, whereas 4 PET scans provided no evidence of disease. Intraoperatively, 13 of 14 FDG-PET/CT-positive localizations of recurrent or persistent thyroid carcinomas were verified and confirmed by histopathology (sensitivity 93%). In another patient lymph node metastases of lung cancer were detected intraoperatively. However, FDG-PET/CT underestimated the number of lesions in 5 of 6 patients undergoing systematic lymphadenectomy. No lymph node or soft tissue metastases were found intraoperatively in 3 of the 4 patients with negative FDG-PET scans. A solitary cystic lymph node metastasis was found in the fourth patient but was not detected by FDG-PET/CT (specificity 75%). FDG-PET/CT has high sensitivity and specificity for the detection of persistent or recurrent differentiated thyroid carcinoma. FDG-PET/CT helps to select patients who might benefit from surgery because it provides precise anatomical details.
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Fluorodesoxiglucosa F18/uso terapéutico , Recurrencia Local de Neoplasia/diagnóstico por imagen , Recurrencia Local de Neoplasia/cirugía , Radiofármacos/uso terapéutico , Neoplasias de la Tiroides/diagnóstico por imagen , Neoplasias de la Tiroides/cirugía , Adenocarcinoma Folicular/diagnóstico por imagen , Adenocarcinoma Folicular/patología , Adenocarcinoma Folicular/secundario , Adenocarcinoma Folicular/cirugía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma/diagnóstico por imagen , Carcinoma/patología , Carcinoma/secundario , Carcinoma/cirugía , Carcinoma Papilar , Femenino , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Imagen Multimodal , Recurrencia Local de Neoplasia/patología , Neoplasia Residual , Tomografía de Emisión de Positrones , Estudios Prospectivos , Reoperación/efectos adversos , Sensibilidad y Especificidad , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides/patología , Tomografía Computarizada por Rayos X , Adulto JovenRESUMEN
A rapid and efficient n.c.a. radiosynthesis of 6-[(11)C]methyldopamine ([(11)C]MeDA) using the Stille cross-coupling reaction as a key step was developed. The labeling conditions for the formation of the intermediate compound (protected [(11)C]MeDA, [(11)C]7) were determined with respect to reaction temperature and time. The radiochemical yield 89 ± 1.4% (decay-corrected) of the protected intermediate [(11)C]7 was obtained at a reaction temperature of 60°C and a reaction time of 5 min using Pd(2)(dba)(3)/P(o-tolyl)(3) and CsF/CuBr as a co-catalyst system. The overall yield after deprotection with 45% HBr at 140°C for 10 min was 64 ± 3.9% (decay-corrected) within a total preparation time of 40 min, including hydrolysis, HPLC purification and formulation.
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Radioisótopos de Carbono/química , Desoxiepinefrina/síntesis química , CalorRESUMEN
Dosimetry is important in the development of radioactive pharmaceuticals, especially for optimizing radionuclide therapy with respect to risk-benefit analysis. To calculate the applied absorbed doses in the target and risk organs standard phantom masses are frequently used. However, deviations to the true organ mass can lead to suboptimal decisions in dose finding studies. To estimate the magnitude of deviations introduced when using standard phantom masses instead of individual organ masses, we investigated 10 patients treated with radioimmunotherapy using (90)Y labelled anti-CD66 antibody. The use of standard phantom masses instead of individually measured organ masses results in mean deviations for liver, spleen and kidneys of 2% (Min. -22%, Max. 34%), -3% (Min. -34, Max. 100%) und -8% (Min. -37, Max. 38%), respectively. For the administered therapeutic activity differences of -16% (Min. -45%, Max. 4%) were observed depending on the used organ mass. These results demonstrate that using standard phantom masses for dosimetry before radionuclide therapy is not adequate.
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Anticuerpos Monoclonales/uso terapéutico , Antígenos CD/inmunología , Moléculas de Adhesión Celular/inmunología , Simulación por Computador , Técnicas Inmunológicas , Radioinmunoterapia/métodos , Planificación de la Radioterapia Asistida por Computador/métodos , Distribución Tisular , Radioisótopos de Itrio/uso terapéutico , Disponibilidad Biológica , Humanos , Fantasmas de Imagen , Radioisótopos de Itrio/farmacocinéticaRESUMEN
UNLABELLED: FDG-PET/CT is increasingly used in staging of lung cancer as single "one stop shop" method. AIM, PATIENTS, METHODS: We prospectively included 104 neurological asymptomatic patients (65 years, 26% women) with primary diagnosis of lung cancer. In all patients PET/CT including cerebral imaging and cerebral MRI were performed. RESULTS: Diagnosis of brain metastases (BM) was made by PET/CT in 8 patients only (7.7%), by MRI in 22 (21.2%). In 80 patients both PET/CT and MRI showed no BM. In 6 patients (5.8%) BM were detectable on PET/CT as well as on MRI. Exclusive diagnosis of BM by MRI with negative finding on PET/CT was present in 16 patients (15.4%). 2 patients (1.9%) had findings typical for BM on PET/CT but were negative on MRI. With MRI overall 100 BM were detected, with PET/CT only 17 BM (p < 0.01). For the diagnosis of BM PET/CT showed a sensitivity of 27.3%, specificity of 97.6%, positive predictive value of 75% and negative predictive value of 83.3%. BM diameter on PET/CT and MRI were consistent in 43%, in 57% BM were measured larger on MRI. DISCUSSION: Compared to the gold standard of MRI for cerebral staging a considerable number of patients are falsely diagnosed as free from BM by PET/CT. MRI is more accurate than PET/CT for detecting multiple and smaller BM. CONCLUSION: In patients with a curative option MRI should be performed additionally to PET/CT for definitive exclusion of brain metastases.
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Neoplasias Encefálicas/epidemiología , Neoplasias Encefálicas/secundario , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/epidemiología , Imagen por Resonancia Magnética/estadística & datos numéricos , Tomografía de Emisión de Positrones/estadística & datos numéricos , Tomografía Computarizada por Rayos X/estadística & datos numéricos , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Encefálicas/diagnóstico , Carcinoma/diagnóstico , Carcinoma/epidemiología , Carcinoma/secundario , Femenino , Fluorodesoxiglucosa F18 , Alemania/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Prevalencia , Radiofármacos , Reproducibilidad de los Resultados , Medición de Riesgo , Factores de Riesgo , Sensibilidad y EspecificidadAsunto(s)
Metástasis de la Neoplasia/patología , Neoplasias de las Paratiroides/patología , Neoplasias Torácicas/secundario , Adenoma/patología , Adenoma/cirugía , Anciano de 80 o más Años , Femenino , Humanos , Metástasis de la Neoplasia/diagnóstico por imagen , Neoplasias de las Paratiroides/cirugía , Tomografía de Emisión de Positrones , Reoperación , Neoplasias Torácicas/diagnóstico por imagen , Neoplasias Torácicas/cirugía , Tomografía Computarizada por Rayos XRESUMEN
OBJECTIVE: Myotonic dystrophy type 1 and 2 (DM1/DM2) are multisystemic diseases with common cognitive deficits beside the cardinal muscular symptoms. We performed a comprehensive analysis of cerebral abnormalities to compare the neuropsychological defects with findings in different imaging methods in the same cohort of patients. METHODS: Neuropsychological investigations, structural cerebral MRI including brain parenchymal fraction (BPF) and voxel-based morphometry (VBM), and (18)F-deoxy-glucose PET (FDG-PET) were performed in patients (20 DM1 and 9 DM2) and matched healthy controls, and analyzed using statistical parametric mapping (SPM2). RESULTS: DM1 and DM2 patients showed typical neuropsychological deficits with a pronounced impairment of nonverbal episodic memory. Both patient groups showed a reduction of the global gray matter (measured by BPF), which could be localized to the frontal and parietal lobes by VBM. Interestingly, VBM revealed a bilateral hippocampal volume reduction that was correlated specifically to both a clinical score and episodic memory deficits. VBM also revealed a pronounced change of thalamic gray matter. White matter lesions were found in >50% of patients and their extent was correlated to psychomotor speed. FDG-PET revealed a frontotemporal hypometabolism, independent of the decrease in cortical gray matter. All abnormalities were similar in both patient groups but more pronounced for DM1. CONCLUSIONS: Our results suggest that 1) some of the characteristic cognitive deficits of these patients are linked to specific structural cerebral changes, 2) decreases in gray matter and metabolism are independent processes, and 3) the widespread brain abnormalities are more pronounced in DM1.
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Encéfalo/diagnóstico por imagen , Encéfalo/patología , Trastornos del Conocimiento/diagnóstico por imagen , Trastornos del Conocimiento/patología , Distrofia Miotónica/complicaciones , Tomografía de Emisión de Positrones/métodos , Adulto , Atrofia/diagnóstico por imagen , Atrofia/metabolismo , Atrofia/patología , Encéfalo/metabolismo , Mapeo Encefálico/métodos , Trastornos del Conocimiento/metabolismo , Progresión de la Enfermedad , Metabolismo Energético/fisiología , Femenino , Fluorodesoxiglucosa F18 , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Persona de Mediana Edad , Fibras Nerviosas Mielínicas/metabolismo , Fibras Nerviosas Mielínicas/patología , Pruebas Neuropsicológicas , Valor Predictivo de las Pruebas , Adulto JovenRESUMEN
Amyloid aggregates play a major role in the development of Alzheimer's disease. Targeting these aggregates by PET probes enables non-invasively the detection and quantification of amyloid deposit distribution in human brains. Based on benzothiazole core structure a series of amyloid imaging agents were developed. Currently [(11)C]2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole (Pittsburgh Compound-B (PIB) is the most specific and widely used amyloid imaging ligand. But due to the short half life of (11)C, longer lived (18)F-labeled derivatives offer logistic advantages and higher contrast images. In this work, three different [(18)F]fluoroethoxy-substituted benzothiazole derivatives ([(18)F]2-(4'-(methylamino)phenyl)-6-(2-fluoroethoxy)benzothiazole, [(18)F]2-((2'-(2-fluoroethoxy)-4'-amino)phenyl)benzothiazole and [(18)F]2-(3'-((2-fluoroethoxy)-4'-amino)phenyl)benzothiazole) were synthesized via [(18)F]fluoroethylation. The latter two derivatives with fluoroethoxy-substitution on the aromatic amino group showed very low binding affinity for amyloid aggregates. In contrast [(18)F]2-(4'-(methylamino)phenyl)-6-(2-fluoroethoxy)benzothiazole with [(18)F]fluoroethoxy-substitution in 6-position showed excellent amyloid imaging properties with respect to lipophilicity, brain entry and brain clearance in normal SCID mice, amyloid plaque binding affinity and specificity.
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Benzotiazoles/síntesis química , Radioisótopos de Flúor , Placa Amiloide/metabolismo , Tomografía de Emisión de Positrones/métodos , Radiofármacos/síntesis química , Enfermedad de Alzheimer/diagnóstico por imagen , Amiloide/metabolismo , Animales , Benzotiazoles/farmacocinética , Encéfalo/metabolismo , Ratones , Ratones SCID , Radiofármacos/farmacocinéticaRESUMEN
In patients with primary hyperparathyroidism (pHPT), positive preoperative localization studies enable to perform a minimally invasive approach for parathyroid surgery. However, current imaging techniques are not always successful. We therefore conducted a study to determine the sensitivity of C-11 methionine positron emission tomography/computed tomography (Met-PET/CT) in localizing parathyroid adenomas in pHPT. Met-PET/CT scans of the neck and mediastinum of 33 patients undergoing parathyroidectomy for primary HPT were compared with intraoperative and histological findings. Primary HPT was caused by a single gland adenoma in 30 patients, while another 3 patients had multiglandular disease. Met-PET/CT scan correctly located a single gland adenoma in 25 out of 30 (83%) patients with pHPT, among them 2 patients with persistent disease, 7 patients with prior neck surgery, and 8 patients with concomitant thyroid nodules. In 3 patients with multiglandular disease, Met-PET/CT showed only one enlarged parathyroid gland in two individuals and was negative in the third patient. Statistical analysis found a significant correlation between true-positive results and the weight (2.42+/-4.05 g) and diameter (2.0+/-1.18 cm) of parathyroid adenomas while the subgroup with false negative findings had significantly smaller (0.98+/-0.54 cm) and lighter (0.5+/-0.38 g) glands. Sensitivity was 83% for single gland adenomas and 67% for multiglandular disease. Met-PET/CT correctly localized 83% of single gland parathyroid adenomas in patients with pHPT. However, preoperative localization of multiglandular disease due to double adenomas or parathyroid hyperplasia remained difficult.
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Adenoma/diagnóstico por imagen , Hiperparatiroidismo Primario/diagnóstico por imagen , Metionina , Neoplasias de las Paratiroides/diagnóstico por imagen , Tomografía de Emisión de Positrones , Tomografía Computarizada por Rayos X , Adenoma/complicaciones , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Hiperparatiroidismo Primario/complicaciones , Cuidados Intraoperatorios , Masculino , Persona de Mediana Edad , Cuello/diagnóstico por imagen , Cuello/cirugía , Neoplasias de las Paratiroides/complicaciones , Cuidados Preoperatorios , Adulto JovenRESUMEN
Adenocarcinomas of the pancreas represent the majority (>95%) of all malignant pancreatic tumors. They are formed from malignant degeneration of the exocrine part of the pancreas. Cystic acinar tumors are much rarer and originate from secretion-producing parenchymal cells of the pancreas. Endocrine tumors of the pancreas will not be dealt with in this context.
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Adenocarcinoma/diagnóstico por imagen , Carcinoma de Células Acinares/diagnóstico por imagen , Carcinoma Ductal Pancreático/diagnóstico por imagen , Procesamiento de Imagen Asistido por Computador , Neoplasias Pancreáticas/diagnóstico por imagen , Tomografía de Emisión de Positrones , Tomografía Computarizada por Rayos X , Adenocarcinoma/patología , Carcinoma de Células Acinares/patología , Carcinoma Ductal Pancreático/patología , Diagnóstico Diferencial , Progresión de la Enfermedad , Fluorodesoxiglucosa F18 , Humanos , Metástasis Linfática/diagnóstico por imagen , Metástasis Linfática/patología , Recurrencia Local de Neoplasia/diagnóstico por imagen , Estadificación de Neoplasias , Páncreas/diagnóstico por imagen , Páncreas/patología , Neoplasias Pancreáticas/patología , Sensibilidad y EspecificidadRESUMEN
AIM: Tumour necrosis factor-alpha (TNF-alpha) serum levels may increase due to intensive conditioning regimes with high-dose-chemotherapy and total body irradiation (TBI) before stem cell transplantation. This increases the risk for developing acute graft versus host disease (aGvHD) after stem cell transplantation. In this prospective study we investigated the influence of radioimmunotherapy with 188Re-CD-66-mAb on changes on TNF-alpha serum levels. PATIENTS, METHODS: In 18 patients we measured TNF-alpha before and up to 96 hours after radioimmunotherapy, in 2 patients in addition following TBI, in 9 patients also following chemotherapy. For measuring TNF-alpha we used an automated immunochemiluminescence assay (Immulite 1000 DPC Biermann, Bad Nauheim). The mean follow up period to record incidence of aGVHD was 100 days after stem cell transplantation. RESULTS: Compared to the basal levels before, the levels of TNF-alpha after conditioning with 188Re-CD-66-mAb did not increase significantly and remained in the physiological range. In contrast, these initial physiological cytokine levels increased and became pathological following 48 h after total body irradiation (13.2+/-6.6 pg/ml) and chemotherapy (10.8+/-15.7 pg/ml). In our study we found a low incidence of aGvHD (22.2%, n=4/18). CONCLUSION: These results demonstrate that additional conditioning therapy with 188Re-CD-66-mAb does not increase proinflammatory cytokine levels of TNF-alpha. This finding may indicate that additive radioimmunotherapy may not be a significant factor for increasing the rate of conditioning-associated aGvHD.
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Leucemia Mieloide Aguda/radioterapia , Síndromes Mielodisplásicos/radioterapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/radioterapia , Radioinmunoterapia/métodos , Radioisótopos/uso terapéutico , Renio/uso terapéutico , Trasplante de Células Madre/métodos , Factor de Necrosis Tumoral alfa/sangre , Adulto , Anticuerpos Monoclonales/uso terapéutico , Antígenos CD/inmunología , Moléculas de Adhesión Celular/inmunología , Niño , Femenino , Humanos , Leucemia Mieloide Aguda/cirugía , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/cirugía , Leucemia-Linfoma Linfoblástico de Células Precursoras/cirugía , Adulto JovenRESUMEN
AIM: [(18)F]fluoro-deoxyglucose positron-emission-tomography (FDG-PET) detects metabolic activity in alveolar echinococcosis (AE). The slow changes in metabolic and morphological characteristics require long-term follow-up of patients. This is the first study to evaluate metabolic activity over may years, hereby assessing the utility of FDG-PET for the evaluation of disease progression and response to treatment. PATIENTS, METHODS: 15 patients received a follow-up FDG-PET combined with computed tomography (integrated PET/CT) with a median of 6.5 years after the first PET in 1999. Number and location of enhanced metabolic activity in the area of AE lesions was determined. Quantification of intensity of metabolic activity was assessed by calculation of mean standardized uptake values. RESULTS: AE lesions in 11/15 patients had been metabolically inactive initially, but only two showed permanent inactivity over the course of 81 months. Interestingly, in two patients metabolic activity was newly detected after 80 and 82 months. Benzimidazole treatment was intermittently discontinued in seven cases. Persisting activity at FDG-PET demanded continued benzimidazole treatment in four patients. Neither treatment duration, lesional size, calcifications nor regressive changes correlated with metabolic activity. CONCLUSION: Treatment responses are heterogeneous and vary from progressive disease despite treatment to long-term inactive disease with discontinued treatment. Lack of metabolic activity indicates suppressed parasite activity and is not equivalent to parasite death. However, metabolic activity may remain suppressed for years, allowing for temporary treatment discontinuation. Relapses are reliably detected with PET and restarting benzimidazole treatment prevents parasite expansion.
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Equinococosis Pulmonar/diagnóstico por imagen , Equinococosis Pulmonar/metabolismo , Fluorodesoxiglucosa F18/farmacocinética , Estudios de Seguimiento , Humanos , Procesamiento de Imagen Asistido por Computador , Tomografía de Emisión de Positrones , Radiofármacos/farmacocinética , Factores de Tiempo , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
BACKGROUND AND OBJECTIVES: Contaminating white blood cells (WBC) contribute remarkably to the overall growth factor content of locally applicable platelet-rich plasma (PRP) or platelet (PLT) gel and change the relative proportions of the contained growth factors. MATERIALS AND METHODS: To study the independent effects of locally applicated highly concentrated PLTs, the development of preparations is needed that contain large amounts of PLTs and no or at least very few leucocytes. Therefore, 20 plateletpheresis procedures were performed in voluntary blood donors to get highly concentrated and extremely WBC-poor plateletpheresis concentrates. The degree of spontaneous PLT activation, the PLT aggregation response to agonists and the level of the growth factor TGF-beta1 (transforming growth factor beta1) were measured immediately after the donation and 1 day later. RESULTS: The concentrates contained 1.96 +/- 0.36 x 10e11 PLTs per unit in 55.2 +/- 7.9 ml, respectively. In comparison to the donors' blood, the PLT-enrichment factor was 15.3 +/- 5.4. At the same time, the concentrates contained extremely low residual numbers of WBCs (0.8 +/- 3.3 x 10e3/ml). The concentration of the growth factor TGF-beta1 was 743.2 +/- 243.9 ng/ml. On day 1, the PLT concentration and the TGF-beta1 content of the PLT concentrates had not decreased. CONCLUSIONS: In summary, plateletpheresis is suited to provide PRP products with higher concentrations of human platelets and platelet-derived growth factors than previously reported PRP preparation methods but with extremely low numbers of contaminating leucocytes.
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Plaquetas/citología , Plaquetoferesis/normas , Recuento de Células Sanguíneas , Plaquetas/metabolismo , Plaquetas/fisiología , Humanos , Leucocitos , Activación Plaquetaria , Agregación Plaquetaria , Factor de Crecimiento Derivado de Plaquetas/análisis , Plaquetoferesis/métodos , Factor de Crecimiento Transformador beta1/análisisRESUMEN
AIM: 5-Iodo-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl) uracil (FIAU) has been used for non-invasive monitoring of gene therapy and as an antiviral agent experimentally and in patients. However, FIAU metabolism in tumor cells is largely unknown. Here, the biological characteristics of FIAU in human leukemia and lymphoma cells in vitro and in a xenotransplant severe combined immunodeficient (SCID)-mouse model were investigated. METHODS: The susceptibility of FIAU to glycosidic bond cleavage by thymidine phosphorylase (TP) and its phosphorylation by human thymidine kinase 1 (hTK1) were examined. Cellular uptake and DNA-incorporation were determined in the leukemia cell line HL60 and the lymphoma cell line DoHH2. Biodistribution, in vivo stability of FIAU and expression of proliferation marker(67)Ki and thymidylate synthase were assessed in SCID-mice bearing HL60 xenotransplants. Cellular distribution of FIAU was imaged by microautoradiography. RESULTS: FIAU proved to be stable against degradation by TP and was phosphorylated by hTK1. Significant cellular uptake in DoHH2 and in HL60 cells was observed. The majority of intracellular [(131)I]FIAU was DNA incorporated. In vivo, moderate dehalogenation of [(131)I]FIAU was observed. Biodistribution studies showed a tumor uptake of 1.8+/-0.4% ID/g after 30 min. The half-life of [(131)I]FIAU in blood was 43+/-2 min. Microautoradiography showed a modest accumulation of [(125)I]FIAU in proliferating cells of small intestine, spleen and tumor. CONCLUSION: Despite phosphorylation by the hTK, efficient incorporation into the DNA and high in vivo stability, FIAU accumulates only moderately and transiently in proliferating cells, suggesting that FIAU is probably not appropriate for imaging of proliferation.
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Antivirales/química , Arabinofuranosil Uracilo/análogos & derivados , ADN/química , Animales , Antivirales/farmacocinética , Arabinofuranosil Uracilo/química , Arabinofuranosil Uracilo/farmacocinética , Línea Celular Tumoral , Química Farmacéutica/métodos , Células HL-60 , Humanos , Ratones , Ratones SCID , Trasplante de Neoplasias , Fosforilación , Timidina Quinasa/metabolismo , Timidina Fosforilasa/metabolismo , Distribución TisularRESUMEN
AIM: Intravascular brachytherapy efficiently reduces vascular smooth muscle cell (SMC) proliferation, interstitial matrix production, vascular remodeling and restenosis rate after revascularization injury of coronary arteries. In this study we examined the molecular mechanisms of the cytotoxic effect of Re-188-mediated beta-irradiation on a SMC culture model compared to that of paclitaxel. METHODS: SMC were irradiated with 1, 3, 10 and 30 Gy with Re-188 or treated with 1, 5, 10 microg/mL paclitaxel. After 24, 48 and 72 h, cell death, apoptosis pathways and cell cycle were examined. RESULTS: Irradiation and paclitaxel induced cell cycle arrest in G1. Dose-dependent cell death ranged from 40% at 1 Gy to 80% at 30 Gy irradiation, and induced in 45% of SMC treated with paclitaxel. Irradiation induced increasing rates of necrotic cell death up to 40% at 30 Gy. Activation of caspase-3 was detected, and poly(ADP-ribose)polymerase (PARP), the prototype substrate of caspases, was cleaved upon beta-irradiation. In addition, beta-irradiation-mediated apoptosis activated caspase-9, indicating that mitochondria were involved. Further-more, Bax was upregulated. However, upregulation of death-inducing ligands (DIL) or receptors (DIL-R) was not involved in beta-irradiation-induced apoptosis in SMC. Similar to beta-irradiation, the intrinsic mitochondrial apoptosis pathway was activated by paclitaxel. CONCLUSION: These findings demonstrate that beta-irradiation and paclitaxel induced apoptosis and activated apoptosis signaling pathways in SMC at several levels by triggering intrinsic mitochondrial but not external death receptor mediated pathways.
Asunto(s)
Apoptosis , Vasos Coronarios/efectos de los fármacos , Vasos Coronarios/patología , Vasos Coronarios/efectos de la radiación , Regulación de la Expresión Génica , Miocitos del Músculo Liso/efectos de los fármacos , Miocitos del Músculo Liso/patología , Miocitos del Músculo Liso/efectos de la radiación , Radioisótopos/química , Renio/química , Muerte Celular , Proliferación Celular , Relación Dosis-Respuesta a Droga , Ligandos , Mitocondrias/metabolismo , Necrosis , Paclitaxel/farmacología , Radiometría , Factores de TiempoRESUMEN
UNLABELLED: AIM of this study was to investigate, how often TNM staging is changed in patients with malignant pleural mesothelioma (MPM) by the application of integrated PET-CT compared to computed tomography alone and how often these changes are clinically relevant. PATIENTS, METHODS: We studied 17 patients (68 +/- 6 years, 8 women) with MPM. Integrated PET-CT scan and histological confirmation were performed in all patients. RESULTS: Final histological diagnosis confirmed 9 epithelial type, 2 sarcomatoid type and 6 biphasic type MPM. Mean standardized uptake value (SUV) was 5.9 +/- 1.9 in epithelial MPM and 15.1 +/- 10.2 in sarcomatoid MPM. CT and PET-CT revealed discordances in 8/17 (47%) patients in TNM classification with 4/8 (50%) being clinically relevant. PET-CT led to downstaging in 5 (29%) and upstaging in 3 (18%) patients. Mean survival time tended to be higher in the subgroup of patients with lower mean SUV. CONCLUSIONS: PET-CT seems to be a valuable tool in staging of MPM and leads to discordant findings in almost every second patient compared to CT alone. In many cases these differences are clinically relevant and have therapeutic consequences.
Asunto(s)
Fluorodesoxiglucosa F18 , Mesotelioma/diagnóstico por imagen , Estadificación de Neoplasias/métodos , Neoplasias Pleurales/diagnóstico por imagen , Radiofármacos , Anciano , Femenino , Humanos , Masculino , Mesotelioma/patología , Persona de Mediana Edad , Neoplasias Pleurales/patología , Radiografía Torácica , Cintigrafía , Tomografía Computarizada por Rayos XRESUMEN
AIM: To evaluate the in vitro and in vivo characteristics of [N-methyl-(11)C]2-(4'-(methylaminophenyl)-benzothiazole ([(11)C]BTA-1) as well as [N-methyl-(11)C]2-(3'-methyl-4'-(methylamino)phenyl)-benzothiazole ([(11)C]3'-Me-BTA-1) as diagnostic markers of amyloid-beta (Abeta) in Alzheimer's disease (AD). MATERIAL, METHODS: Brain uptake and clearance was determined in wild-type mice. Binding affinities (K(i)) of [(11)C]BTA-1 and [(11)C]3'-Me-BTA-1 for aggregated Abeta(1-40) fibrils were assessed. Autoradiography was performed on brain sections of AD patients. To demonstrate binding specificity in vivo BTA-1 was injected i.p. in transgenic mice (Tg2576). Brain sections were analysed consecutively. Additionally, a [(11)C]BTA-1 PET study of an AD patient and a healthy control was performed. RESULTS: In mice brain uptake and clearance of [(11)C]BTA-1 is compatible with the half life of (11)C (2 min: 12.7 % ID/g; 30 min: 4.6% ID/g). In contrast clearance rate of [(11)C]3'-Me-BTA-1 is too slow (2 min 4% ID/g; 30 min 12% ID/g) to achieve sufficient clearance of free and non specifically bound radioactivity. K(i) of [(11)C]BTA-1 is 11 nmol/l and that of [(11)C]3'-Me-BTA-1 27 nmol/l. Both radioligands label Abeta selectively and specifically in AD patients and transgenic mice in vitro. The in vivo stained brain sections show a labelling of Abeta plaques. The AD patient has a higher prefrontal, parietal and striatal [(11)C]BTA-1 accumulation than the healthy control. Metabolite analysis revealed approximately 75% intact [(11)C]BTA-1 after 30min in plasma.[(11)C]BTA-1 is favourable for in vivo imaging of Abeta due to its rapid brain entry, sufficient clearance and good binding affinity for Abeta. CONCLUSION: The ability to label Abeta plaques in vivo in human subjects supports the suitability of [(11)C]BTA-1 as a plaque imaging agent.
Asunto(s)
Enfermedad de Alzheimer/diagnóstico por imagen , Péptidos beta-Amiloides/metabolismo , Benzotiazoles/farmacocinética , Encéfalo/diagnóstico por imagen , para-Aminobenzoatos , Ácido 4-Aminobenzoico/síntesis química , Ácido 4-Aminobenzoico/farmacocinética , Animales , Transporte Biológico , Encéfalo/metabolismo , Encéfalo/patología , Radioisótopos de Carbono/farmacocinética , Humanos , Ratones , Ratones Transgénicos , Tomografía de Emisión de Positrones , Radiofármacos/farmacocinéticaRESUMEN
Prostate carcinoma is the most common life-threatening cancer affecting men in the western world. In Germany about 40,600 new cases have to be expected each year. The mortality is around 10%. The major goals of pretherapeutic imaging are to determine the local extent of prostate carcinoma in terms of intraprostate localisation, extracapsular extension (ECE), seminal vesicle invasion (SVI), tumour infiltration into neurovascular bundles, and if this has taken place, into surrounding tissues and organs in the small pelvis, detection of loco-regional metastases via the lymph nodes and of this so, of distant metastases. Exact pretherapeutic diagnosis and staging are essential, because the tumour treatment must be selected in strict dependence on clinical tumour stage and risk profile. Both anatomic and functional molecular imaging of prostate carcinoma have advanced significantly in recent years. When there are problems with diagnosis, e.g. when prostate punch biopsies are negative while the suspicion of prostate carcinoma persists, C-11/F-18 choline PET/CT and MRT/MRS may be helpful in localising the carcinoma, revealing how the carcinoma relates to the surrounding intra- and extraprostatic structures and organs, and making a targeted repeat biopsy possible. Lymphotropic contrast agents are highly promising for accurate nodal staging of prostate carcinoma, but are not yet available for routine clinical use; In these circumstances, the sensitivity of nodal staging with the widely available imaging modalities remains inadequate, and its specificity is also less than optimal. There has been particularly substantial progress in the localisation of local relapse, which can be imaged with contrast-enhanced C-11-choline PET/CT and MRT in most cases when PSA is >0.5-1 ng/ml. 18F-Fluoride PET/CT has proved accurate in the diagnosis of skeletal metastases from prostate carcinoma.