[Ionizing radiation received by patients with osteosarcoma during intra-arterial chemotherapy treatment]. / Radiación ionizante recibida por pruebas de radiología intervencionista durante el tratamiento con quimioterapia intraarterial en pacientes afectos de osteosarcoma.

BACKGROUND: Osteosarcoma paediatric patients are usually treated with intra-arterial chemotherapy (QTia) which is admi-nistered directly to the tumour. This procedure exposes patients to ionizing radiation. Paediatric patients are especially sensitive to this exposure. METHODS: The total amount of ionizing radiation received from QTia administration was quantified in a group of 16 osteo-sarcoma paediatric patients from the Clínica Universidad de Navarra. RESULTS: The median of the total radiation received per patient was 33.4 Gy·cm2 (IQR: 43.33 Gy·cm2), and the median number of procedures performed per subject was 10 (IQR: 6.5). CONCLUSIONS: The study highlights the importance of quantifying the radiation received by a group of children and adoles-cents affected by osteosarcoma during treatment with QTia. Long-term side effects of this radiation should be considered in pae-diatric patients. Currently, there are no previous studies that provide data of the amount of ionizing radiation received through this procedure.

Radiation dose produced by patients during radiopharmaceutical incorporation in nuclear medicine diagnostic procedures.

OBJECTIVES: The aim of this study was to assess the dose received by members of the public due to close contact with patients undergoing nuclear medicine procedures during radiopharmaceutical incorporation, and comparing it with the emitted radiation dose when the test was complete, in order to establish recommendations. MATERIAL AND METHODS: A prospective study was conducted on 194 patients. H*(10) dose rates were measured at 0.1, 0.5, and 1.0m after the radiopharmaceutical administration, before the image acquisition, and at the end of the nuclear medicine procedure. Effective dose for different close contact scenarios were calculated, according to 95th percentile value (bone scans) and the maximum value (remaining tests). RESULTS: During the radiopharmaceutical incorporation, a person who stays with another injected patient in the same waiting room may receive up to 0.59 mSv. If the patient had a medical appointment, or went to a restaurant or a coffee shop, members of the public could receive 23, 43, and 22 µSv, respectively. After finishing the procedure, these doses are reduced by a factor 3. In most of the studies, the use of private instead of public transport may reduce the dose by more than a factor 6. CONCLUSION: It is recommended to increase the distance between the patients during the radiopharmaceutical incorporation and to distribute them according to the diagnostic procedure. Patients should be encouraged to use private instead of public transport. Depending on the number of nuclear medicine outpatients per year attended by a physician, it could be necessary to apply restrictions.

Radiation dosimetry and biodistribution in non-human primates of the sodium/iodide PET ligand [(18)F]-tetrafluoroborate.

BACKGROUND: [(18)F]-tetrafluoroborate is a PET radiotracer taken up by the sodium/iodide symporter (NIS). Albeit the in vivo behavior in rodents is similar to the (99m)Tc-pertechnetate, no studies exist in primates or in humans. The aims of this study were to evaluate the biodistribution of [(18)F]-tetrafluoroborate in non-human primates with PET and to estimate the absorbed dose in organs. METHODS: Whole-body PET imaging was done in a Siemens ECAT HR+ scanner in two male Macaca fascicularis monkeys. After an i.v. injection of 24.93 ± 0.05 MBq/kg of [(18)F]-tetrafluoroborate, prepared by isotopic exchange of sodium tetrafluoroborate with [(18)F]-fluoride under acidic conditions, eight sequential images from the head to the thigh (five beds) were collected for a total duration of 132 min. The whole-body emission scan was reconstructed applying attenuation and scatter corrections. After image reconstruction, three-dimensional volumes of interest (VOIs) were hand-drawn on the PET transaxial or coronal slices of the frame where the organ was most conspicuous. Time-activity curves for each VOI were obtained, and the organ residence times were calculated by integration of the time-activity curves. Human absorbed doses were estimated using the OLINDA/EXM software and the standard human model. RESULTS: [(18)F]-tetrafluoroborate was able to discriminate clearly the thyroid gland with an excellent signal-to-noise ratio. Most of the radiotracers (residence time) are localised in the organs that express NIS (stomach wall, salivary glands, thyroid, olfactory mucosa), are involved in excretion (kidneys and bladder), or reflect the vascular phase (heart and lungs). Considering the OLINDA source organs, the critical organs were the stomach wall, thyroid and bladder wall, with absorbed doses lower than 0.078 mGy/MBq. The effective dose was 0.025 mSv/MBq. CONCLUSIONS: [(18)F]-tetrafluoroborate is a very useful radiotracer for PET thyroid imaging in primates, with a characteristic biodistribution in organs expressing NIS. It delivers an effective dose slightly higher than the dose produced by (99m)Tc-pertechnetate but much lower than that produced by radioiodine in the form of (131)INa, (123)INa, or (124)INa.

[¹8F]fluorothymidine-positron emission tomography in patients with locally advanced breast cancer under bevacizumab treatment: usefulness of different quantitative methods of tumor proliferation.

OBJECTIVES: To investigate quantitative methods of tumor proliferation using 3'-[(18)F]fluoro-3'-deoxythymidine ([(18)F]FLT) PET in patients with breast cancer (BC), studied before and after one bevacizumab administration, and to correlate the [(18)F]FLT-PET uptake with the Ki67 index. MATERIAL AND METHODS: Thirty patients with newly diagnosed, untreated BC underwent a [(18)F]FLT-PET before and 14 days after bevacizumab treatment. A dynamic scan centered over the tumor began simultaneously with the injection of [(18)F]FLT (385 ± 56 MBq). Image derived input functions were obtained using regions of interest drawn on the left ventricle (LV) and descending aorta (DA). Metabolite corrected blood curves were used as input functions to obtain the kinetic Ki constant using the Patlak graphical analysis (time interval 10-60 min after injection). Maximum SUV values were derived for the intervals 40-60 min (SUV40) and 50-60 min (SUV50). PET parameters were correlated with the Ki67 index obtained staining tumor biopsies. RESULTS: [(18)F]FLT uptake parameters decreased significantly (p<0.001) after treatment: SUV50=3.09 ± 1.21 vs 2.22 ± 0.96; SUV40=3.00 ± 1.18 vs 2.14 ± 0.95, Ki_LV(10-3)=52[22-116] vs 38[13-80] and Ki_DA(10-3)=49[15-129] vs 33[11-98]. Consistency interclass correlation coefficients within SUV and within Ki were high. Changes of SUV50 and Ki_DA between baseline PET and after one bevacizumab dose PET correlated with changes in Ki67 index (r-Pearson=0.35 and 0.26, p=0.06 and 0.16, respectively). CONCLUSIONS: [(18)F]FLT-PET is useful to demonstrate proliferative changes after a dose of bevacizumab in patients with BC. Quantification of tumor proliferation by means of SUV and Ki has shown similar results, but SUV50 obtained better results. A correlation between [(18)F]FLT changes and Ki67 index was observed.

[Validation of segmentation techniques for positron emission tomography using ex-vivo images of oncological surgical specimens]. / Validación de técnicas de segmentación para la tomografía por emisión de positrones mediante imágenes ex-vivo de piezas quirúrgicas oncológicas.

OBJECTIVE: To design a novel ex-vivo acquisition technique to establish a common framework to validate different segmentation techniques for oncological PET images. To evaluate several automatic segmentation algorithms on this set of images. MATERIAL AND METHODS: In 15 patients with cancer, ex-vivo PET studies of surgical specimens removed during surgery were performed after injection of (18)F-FDG. Images were acquired in two scanners: a clinical PET/CT and a high-resolution PET scanner. Real tumor volume was determined in each patient, and a reference image was generated for segmentation of each tumor. Images were segmented with 12 automatic algorithms and with a standard method for PET (relative threshold at 42%) and results were evaluated by quantitative parameters. RESULTS: It has been possible to demonstrate by segmentation of PET images of surgical specimens that on high resolution PET images, 8 out of 12 evaluated segmentation techniques outperformed the standard method, whose value is 42%. However, none of the algorithms outperformed the standard method when applied on images from the clinical PET/CT. Due to the great interest of this set of PET images, all studies have been published on the Internet in order to provide a common framework for validation and comparison of different segmentation techniques. CONCLUSIONS: We have proposed a novel technique to validate segmentation techniques for oncological PET images, acquiring ex-vivo PET studies of surgical specimens. We have demonstrated the usefulness of this set of PET images by evaluating several automatic segmentation algorithms.

Automated analysis of FDG PET as a tool for single-subject probabilistic prediction and detection of Alzheimer's disease dementia.

PURPOSE: To introduce, evaluate and validate a voxel-based analysis method of ¹8F-FDG PET imaging for determining the probability of Alzheimer's disease (AD) in a particular individual. METHODS: The subject groups for model derivation comprised 80 healthy subjects (HS), 36 patients with mild cognitive impairment (MCI) who converted to AD dementia within 18 months, 85 non-converter MCI patients who did not convert within 24 months, and 67 AD dementia patients with baseline FDG PET scan were recruited from the AD Neuroimaging Initiative (ADNI) database. Additionally, baseline FDG PET scans from 20 HS, 27 MCI and 21 AD dementia patients from our institutional cohort were included for model validation. The analysis technique was designed on the basis of the AD-related hypometabolic convergence index adapted for our laboratory-specific context (AD-PET index), and combined in a multivariable model with age and gender for AD dementia detection (AD score). A logistic regression analysis of different cortical PET indexes and clinical variables was applied to search for relevant predictive factors to include in the multivariable model for the prediction of MCI conversion to AD dementia (AD-Conv score). The resultant scores were stratified into sixtiles for probabilistic diagnosis. RESULTS: The area under the receiver operating characteristic curve (AUC) for the AD score detecting AD dementia in the ADNI database was 0.879, and the observed probability of AD dementia in the six defined groups ranged from 8% to 100% in a monotonic trend. For predicting MCI conversion to AD dementia, only the posterior cingulate index, Mini-Mental State Examination (MMSE) score and apolipoprotein E4 genotype (ApoE4) exhibited significant independent effects in the univariable and multivariable models. When only the latter two clinical variables were included in the model, the AUC was 0.742 (95% CI 0.646 - 0.838), but this increased to 0.804 (95% CI 0.714 - 0.894, bootstrap p=0.027) with the addition of the posterior cingulate index (AD-Conv score). Baseline clinical diagnosis of MCI showed 29.7% of converters after 18 months. The observed probability of conversion in relation to baseline AD-Conv score was 75% in the high probability group (sixtile 6), 34% in the medium probability group (merged sixtiles 4 and 5), 20% in the low probability group (sixtile 3) and 7.5% in the very low probability group (merged sixtiles 1 and 2). In the validation population, the AD score reached an AUC of 0.948 (95% CI 0.625 - 0.969) and the AD-Conv score reached 0.968 (95% CI 0.908 - 1.000), with AD patients and MCI converters included in the highest probability categories. CONCLUSION: Posterior cingulate hypometabolism, when combined in a multivariable model with age and gender as well as MMSE score and ApoE4 data, improved the determination of the likelihood of patients with MCI converting to AD dementia compared with clinical variables alone. The probabilistic model described here provides a new tool that may aid in the clinical diagnosis of AD and MCI conversion.

[Contribution of time of flight and point spread function modeling to the performance characteristics of the PET/CT Biograph mCT scanner]. / Aportación del tiempo de vuelo y de la modelización de la respuesta a una fuente puntual a las características de funcionamiento del tomógrafo PET/TAC Biograph mCT.

OBJECTIVE: To characterize the performance of the Biograph mCT PET/CT TrueV scanner with time of flight (TOF) and point spread function (PSF) modeling. MATERIAL AND METHODS: The PET/CT scanner combines a 64-slice CT and PET scanner that incorporates in the reconstruction the TOF and PSF information. PET operating characteristics were evaluated according to the standard NEMA NU 2-2007, expanding some tests. In addition, different reconstruction algorithms were included, and the intrinsic radiation and tomographic uniformity were also evaluated. RESULTS: The spatial resolution (FWHM) at 1 and 10cm was 4.4 and 5.3mm, improving to 2.6 and 2.5mm when PSF is introduced. Sensitivity was 10.9 and 10.2 Kcps/MBq at 0 and 10cm from the axis. Scatter fraction was less than 34% at low concentrations and the noise equivalent count rate (NECR) was maximal at 27.8 kBq/mL with 182 Kcps, the intrinsic radiation produced a rate of 4.42 true coincidences per second. Coefficient of variation of the volume and system uniformity were 4.7 and 0.8% respectively. The image quality test showed better results when PSF and TOF were included together. PSF improved the hot spheres contrast and background variability, while TOF improved the cold spheres contrast. CONCLUSIONS: The Biograph mCT TrueV scanner has good performance characteristics. The image quality improves when the information from the PSF and the TOF is incorporated in the reconstruction.

Quantitative volumetric analysis of gliomas with sequential MRI and ¹¹C-methionine PET assessment: patterns of integration in therapy planning.

PURPOSE: The aim of the study was to evaluate the volumetric integration patterns of standard MRI and (11)C-methionine positron emission tomography (PET) images in the surgery planning of gliomas and their relationship to the histological grade. METHODS: We studied 23 patients with suspected or previously treated glioma who underwent preoperative (11)C-methionine PET because MRI was imprecise in defining the surgical target contour. Images were transferred to the treatment planning system, coregistered and fused (BrainLAB). Tumour delineation was performed by (11)C-methionine PET thresholding (vPET) and manual segmentation over MRI (vMRI). A 3-D volumetric study was conducted to evaluate the contribution of each modality to tumour target volume. All cases were surgically treated and histological classification was performed according to WHO grades. Additionally, several biopsy samples were taken according to the results derived either from PET or from MRI and analysed separately. RESULTS: Fifteen patients had high-grade tumours [ten glioblastoma multiforme (GBM) and five anaplastic), whereas eight patients had low-grade tumours. Biopsies from areas with high (11)C-methionine uptake without correspondence in MRI showed tumour proliferation, including infiltrative zones, distinguishing them from dysplasia and radionecrosis. Two main PET/MRI integration patterns emerged after analysis of volumetric data: pattern vMRI-in-vPET (11/23) and pattern vPET-in-vMRI (9/23). Besides, a possible third pattern with differences in both directions (vMRI-diff-vPET) could also be observed (3/23). There was a statistically significant association between the tumour classification and integration patterns described above (p < 0.001, κ = 0.72). GBM was associated with pattern vMRI-in-vPET (9/10), low-grade with pattern vPET-in-vMRI (7/8) and anaplastic with pattern vMRI-diff-vPET (3/5). CONCLUSION: The metabolically active tumour volume observed in (11)C-methionine PET differs from the volume of MRI by showing areas of infiltrative tumour and distinguishing from non-tumour lesions. Differences in (11)C-methionine PET/MRI integration patterns can be assigned to tumour grades according to the WHO classification. This finding may improve tumour delineation and therapy planning for gliomas.

Neuroimagen: fundamentos técnicos y prácticos / Neuroimaging: technical aspects and practice

Las pruebas de neuroimagen funcional y estructural como la tomografía por emisión de positrones (PET), tomografía por emisión de fotón único (SPECT), tomografía computerizada (CT) y resonancia magnética (RM) aportan una información complementaria de gran importancia para el diagnóstico y el tratamiento de pacientes con trastornos del sistema nervioso central. Prueba de ello es su aplicación rutinaria en la práctica clínica y en la investigación biomédica. En los últimos años hemos asistido al desarrollo de equipos multimodalidad que permiten realizar un estudio PET o SPECT con una imagen estructural de CT, y más recientemente, equipos experimentales que combinan la técnica PET y la RM. Adicionalmente se han perfeccionado aspectos tanto metodológicos que aportan una mayor calidad de imagen, como de técnicas de análisis para una cuantificación e interpretación objetiva. En este artículo se revisan los fundamentes técnicos de dichas modalidades de imagen; destacando los avances más significativos y recientes en el desarrollo de estos equipos(AU)

Neuroimaging using both functional and structural examinations like positron emission tomography (PET), single photon emission tomography (SPECT), computed tomography (CT) and magnetic nuclear imaging (MRI) provide supportive information of great importance for the diagnosis and treatment of patients with central nervous system disorders. Therefore, they have become commonplace in clinical practice and basic biomedical research. In recent years we have seen the development of multimodality equipment that enables PET or SPECT to be combined with a CT structural image. Moreover, experimental equipment combining PET and MRI has now been developed. Additionally, methodological features that provide a higher image quality, and analysis tools for objective quantification and interpretation have been refined. This article reviews the technical aspects of those imaging methods, highlighting the most significant and recent advances in the development of neuroimaging(AU)

[Neuroimaging: technical aspects and practice]. / Neuroimagen: Fundamentos técnicos y prácticos.

Neuroimaging using both functional and structural examinations like positron emission tomography (PET), single photon emission tomography (SPECT), computed tomography (CT) and magnetic nuclear imaging (MRI) provide supportive information of great importance for the diagnosis and treatment of patients with central nervous system disorders. Therefore, they have become commonplace in clinical practice and basic biomedical research. In recent years we have seen the development of multimodality equipment that enables PET or SPECT to be combined with a CT structural image. Moreover, experimental equipment combining PET and MRI has now been developed. Additionally, methodological features that provide a higher image quality, and analysis tools for objective quantification and interpretation have been refined. This article reviews the technical aspects of those imaging methods, highlighting the most significant and recent advances in the development of neuroimaging.

Evaluation of spatial resolution of a PET scanner through the simulation and experimental measurement of the recovery coefficient.

PURPOSE: In order to measure spatial resolution of a PET tomograph in clinical conditions, this study describes and validates a method based on the recovery coefficient, a factor required to compensate underestimation in measured radioactivity concentration for small structures. METHODS: In a PET image, the recovery factors of radioactive spheres were measured and their comparison with simulated recovery coefficients yielded the tomographic spatial resolution. Following this methodology, resolution was determined in different surrounding media and several conditions for reconstruction, including clinical conditions for brain PET studies. All spatial resolution values were compared with those obtained using classical methods with point and line sources. RESULTS: In each considered condition, spatial resolution of the PET image estimated using the recovery coefficient showed good agreement with classical methods measurements, validating the procedure. CONCLUSION: Measurement of the recovery coefficient provides an assessment of tomographic spatial resolution, particularly in clinical studies conditions.

New MRI, 18F-DOPA and 11C-(+)-alpha-dihydrotetrabenazine templates for Macaca fascicularis neuroimaging: advantages to improve PET quantification.

Normalization of neuroimaging studies to a stereotaxic space allows the utilization of standard volumes of interest (VOIs) and voxel-based analysis (SPM). Such spatial normalization of PET and MRI studies requires a high quality template image. The aim of this study was to create new MRI and PET templates of (18)F-DOPA and (11)C-(+)-alpha-dihydrotetrabenazine ((11)C-DTBZ) of the Macaca fascicularis brain, an important animal model of Parkinson's disease. MRI template was constructed as a smoothed average of the scans of 15 healthy animals, previously transformed into the space of one representative MRI. In order to create the PET templates, (18)F-DOPA and (11)C-DTBZ PET of the same subjects were acquired in a dedicated small animal PET scanner and transformed to the created MRI template space. To validate these templates for PET quantification, parametric values obtained with a standard VOI-map applied after spatial normalization to each template were statistically compared to results computed using individual VOIs drawn for each animal. The high correlation between both procedures validated the utilization of all the templates, improving the reproducibility of PET analysis. To prove the utility of the templates for voxel-based quantification, dopamine striatal depletion in a representative monkey treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was assessed by SPM analysis of (11)C-DTBZ PET. A symmetric reduction in striatal (11)C-DTBZ uptake was detected in accordance with the induced lesion. In conclusion, templates of M. fascicularis brain have been constructed and validated for reproducible and automated PET quantification. All templates are electronically available via the internet.

Evaluation of CdZnTe as neutron detector around medical accelerators.

The operation of electron linear accelerators (LINACs) and cyclotrons can produce a mixed gamma-neutron field composed of energetic neutrons coming directly from the source and scattered lower energy neutrons. The thermal neutron detection properties of a non-moderated coplanar-grid CdZnTe (CZT) gamma-ray detector close to an 18 MV electron LINAC and an 18 MeV proton cyclotron producing the radioisotope (18)F for positron emission tomography are investigated. The two accelerators are operated at conditions producing similar thermal neutron fluence rates of the order of 10(4) cm(-2) s(-1) at the measurement locations. The counting efficiency of the CZT detector using the prompt 558 keV photopeak following (113)Cd thermal neutron capture is evaluated and a good neutron detection performance is found at the two installations.

[Use of 11C-(+)-alpha -dihydrotetrabenazine for the assessment of dopaminergic innervation in animal models of Parkinson's disease]. / Utilización de la 11C-(+)-alpha -dihidrotetrabenazina para la evaluación de la inervación dopaminérgica en modelos animales de la enfermedad de Parkinson.

AIM: This study evaluates the utility of (11)C-(+)-alpha -dihydrotetrabenazine ((11)C-(+)DTBZ) in the quantification of dopaminergic innervation by positron emission tomography (PET) in rat and monkey, two animal species used as animal models of Parkinson's disease. MATERIAL AND METHODS: Healthy control animals (n = 10) and the effect of 6-hydroxidopamine (6-OHDA) neurotoxic were studied in rats. (18)F-DOPA PET studies and digital quantitative autoradiography were also carried out. Studies with Macaca fascicularis were performed in control and 1-methyl 4-phenyl 1, 2, 3, 6-tetrahydropyridine (MPTP) treated animals. RESULTS: In both species high quality images were generated in which clear uptake of (11)C-(+)DTBZ was found in the striatum. (11)C-(+)DTBZ uptake quantification was estimated by creating parametric images and binding potential (BP) calculation. BP in control rats was 1.10 +/- 0.16 (mean +/- standard deviation [SD], whereas 6-OHDA produced a decrease in the uptake depending on the lesion degree. Images obtained with (18)F-DOPA were not adequate for the analysis as they did not discriminate the stratum whereas digital quantitative autoradiography studies confirmed the high affinity of striatum by (11)C-(+)DTBZ. In monkeys, final BP values were 1.31 and 1.06 and MPTP treatment reduced uptake by 40 %. CONCLUSIONS: The quality of PET images and the decrease of uptake in 6-OHDA and MPTP lesions show that (11)C-(+)DTBZ is an adequate radiotracer for the study of dopaminergic innervation in these animal models.

Utilización de la 11C-(+)-α -dihidrotetrabenazina para la evaluación de la inervación dopaminérgica en modelos animales de la enfermedad de Parkinson / Use of 11C-(+)-α -dihydrotetrabenazine for the assessment of dopaminergic innervation in animal models of Parkinson’s disease

Objetivo. Este trabajo evalúa la idoneidad del radiotrazador 11C-(+)-α -dihidrotetrabenazina (11C-(+)DTBZ) para cuantificar mediante tomografía de emisión de positrones (PET) la inervación dopaminérgica en rata y mono, especies utilizadas como modelos animales en el estudio de la enfermedad de Parkinson. Material y métodos. En ratas se estudió una población control sana (n = 10) y el efecto del neurotóxico 6-hidroxidopamina (6-OHDA), además de realizarse estudios PET con 6-[(18)F]-fluoro-L-DOPA (18F-DOPA) y de autorradiografía digital cuantitativa. El estudio en Macaca fascicularis se realizó en animales control y tratados con el tóxico 1-metil-4-fenil-1,2,3,6-tetrahidropiridina (MPTP). Resultados. En ambas especies se obtuvieron imágenes de gran calidad donde se observó una alta captación de 11C-(+) DTBZ en el estriado. La cuantificación se realizó mediante la creación de imágenes paramétricas y el cálculo del potencial de unión (BP). La medida del BP en la población control de ratas arrojó un valor de 1,10 ± 0,16 (media ± error estándar [EE]), mientras que los estriados dañados con 6-OHDA mostraron una captación disminuida en función del grado de la lesión. Las imágenes obtenidas con 18F-DOPA no fueron aptas para el análisis al no discriminar los estriados, mientras que el estudio mediante autorradiografía digital cuantitativa confirmó la elevada afinidad de la 11C-(+)DTBZ por estas estructuras. En monos, el valor final de BP fue de 1,31 y 1,06 mientras que el tratamiento con MPTP disminuyó la captación en un 40 %. Conclusiones. La calidad de las imágenes PET y la disminución de la captación en las lesiones con 6-OHDA y MPTP indican que la 11C-(+)DTBZ es un radiotrazador adecuado para el estudio de la inervación dopaminérgica en estas especies animales

Aim. This study evaluates the utility of 11C-(+)-α -dihydrotetrabenazine (11C-(+)DTBZ) in the quantification of dopaminergic innervation by positron emission tomography (PET) in rat and monkey, two animal species used as animal models of Parkinson's disease. Material and methods. Healthy control animals (n = 10) and the effect of 6-hydroxidopamine (6-OHDA) neurotoxic were studied in rats. 18F-DOPA PET studies and digital quantitative autoradiography were also carried out. Studies with Macaca fascicularis were performed in control and 1-methyl 4-phenyl 1, 2, 3, 6-tetrahydropyridine (MPTP) treated animals. Results. In both species high quality images were generated in which clear uptake of 11C-(+)DTBZ was found in the striatum. 11C-(+)DTBZ uptake quantification was estimated by creating parametric images and binding potential (BP) calculation. BP in control rats was 1.10 ± 0.16 (mean ± standard deviation [SD], whereas 6-OHDA produced a decrease in the uptake depending on the lesion degree. Images obtained with 18F-DOPA were not adequate for the analysis as they did not discriminate the stratum whereas digital quantitative autoradiography studies confirmed the high affinity of striatum by 11C-(+)DTBZ. In monkeys, final BP values were 1.31 and 1.06 and MPTP treatment reduced uptake by 40 %. Conclusions. The quality of PET images and the decrease of uptake in 6-OHDA and MPTP lesions show that 11C-(+)DTBZ is an adequate radiotracer for the study of dopaminergic innervation in these animal models

[Quick and simple synthesis of (11)C-(+)-alpha-dihydrotetrabenazine to be used as a PET radioligand of vesicular monoamine transporters]. / Síntesis rápida y simplificada de C-(+)-alpha-dihidrotetrabenazina para su utilización como radioligando PET de los transportadores vesiculares de monoaminas.

UNLABELLED: Dihydrotetrabenazine (2-hydroxy-3-isobutyl-9,10-dimethoxy-1,3,4,6,7-hexahydro-11bH-benzo[a]-quinolizine, DTBZ) has become the ideal radioligand for the presynaptic vesicular monoamine transporter VMAT2 based on its high binding affinity and optimal lipophilicity. OBJECTIVE: To develop an automatic procedure for labelling DTBZ with carbon-11, which has been shown to be a highly effective marker for in vivo studies of neuronal losses in animal models with Parkinson's disease using positron emission tomography (PET). MATERIALS AND METHODS: We have developed a new fully automated synthesis procedure to obtain 11C-(+)DTBZ quickly and simply through labelling the precursor -(+)desmethyldihy-drotetrabenazine- at room temperature in the presence of dimethyl sulfoxide (DMSO) and potassium hydroxide (KOH), using 11CH3I as primary precursor. The final purification was carried out by solid phase extraction using commercially available cartridges and the residual solvents (DMSO and ethyl ether) were eliminated by evaporation. RESULTS: The whole procedure was automated, and after 54 syntheses, an average production of 1.94 GBq of sterile, pyrogen-free 11C-(+)DTBZ with a radiochemical purity > 99 % was obtained with 5 minutes irradiation and 6 minutes of synthesis after 11CH3I production. 11C-(+)DTBZ binding to presynaptic dopamine nerve terminals has been demonstrated by MicroPET studies in Wistar rats and M. Fascicularis monkeys. CONCLUSIONS: This new synthesis procedure is quick and simple, due to optimised techniques, which have allowed elimination of residual solvents based on their polarity for the final purification. It is also applicable to other automatic syntheses for obtaining compounds labelled by methylation reactions.

18F-FDG metabolism in a rat model of chronic infarction: a 17-sector semiquantitative analysis.

UNLABELLED: Strategies to establish the functional benefit of cell therapy in cardiac regeneration and the potential mechanism are needed. AIMS: Development of a semi-quantitative method for non invasive assessment of cardiac viability and function in a rat model of myocardial infarction (MI) based on the use of microPET. ANIMALS, METHODS: Ten rats were subjected to myocardial imaging 2, 7, 14, 30, 60 and 90 days after left coronary artery ligation. Intravenous 18F-fluoro-2-deoxy-2-D-glucose (18F-FDG) was administered and regional 18F activity concentrations per unit area were measured in 17 regions of interest (ROIs) drawn on cardiac polar maps. By comparing the differences in 18F uptake between baseline and each of the follow up time points, parametric polar maps of statistical significance (PPMSS) were calculated. Left ventricular ejection fraction (LVEF) was blindly assessed echocardiographically. All animals were sacrificed for histopathological analysis after 90 days. RESULTS: The diagnostic quality of 18F-FDG microPET images was excellent. PPMSS demonstrated a statistically significant decrease in 18F concentrations as early as 48 hours after MI in 4 of the 17 ROIs (segments 7, 13, 16 and 17; p < 0.05) that persisted throughout the study. Semiquantitative analysis of 18F-FDG uptake correlated with echocardiographic decrease in LVEF (p < 0.001). CONCLUSION: The use of PPMSS based on 18F-FDG-microPET provides valuable semi-quantitative information of heart glucose metabolism allowing for non-invasive follow up thus representing a useful strategy for assessment of novel therapies in cardiac regeneration.

Neutron spectrometry in a PET cyclotron with a Bonner sphere system.

Positron emission tomography (PET) is a non-invasive medical imaging technique normally used for diagnostic purposes to determine the location and concentration of physiologically active compounds in a human body. An unshielded cyclotron is used for PET at the Clinica Universitaria de Navarra to produce short-lived positron emitting radionuclides ((15)O, (13)N, (11)C and (18)F) by bombarding appropriate target material with proton or deuteron beams with energies up to 18 and 9 MeV, respectively. Subsequent nuclear reactions may generate undesirable neutrons that should be evaluated and controlled. In this study, the neutron measurements performed with an active and a passive Bonner sphere systems at different locations outside and inside the cyclotron vault during operation have been presented. The neutron spectrum at each location was determined with an unfolding code developed by the authors.

Monte Carlo neutron doses estimations inside a PET cyclotron vault room.

Neutron organ equivalent doses, effective doses and dose equivalents received inside a positron emission tomography vault room in a maximum credible accident have been estimated with the Monte Carlo code MCNPX. While an operator was inside the vault room of a Cyclone 18/9 IBA cyclotron, this was producing (18)F with 30 muA proton current in the target and the operator had to activate a stopped emergency device placed on the wall. MC simulation of the cyclotron vault were carried out to estimate the organ and tissue equivalent doses in a mathematical male mannequin simulating the operator facing the wall on which the emergency device is placed. Doses were calculated at two emergency devices for each one of the two targets of the cyclotron, which were able to produce (18)F. The maximum effective dose in the mannequin was 6.70 Sv/h and the maximum organ equivalent dose was 18.47 Sv/h in spleen.

Study of the neutron field in the vicinity of an unshielded PET cyclotron.

The neutron field in the proximity of an unshielded PET cyclotron was investigated during 18F radioisotope production with an 18 MeV proton beam. Thermoluminescent detector (TLD) models TLD600 and TLD700 as well as Bonner moderating spheres were irradiated at different positions inside the vault room where the cyclotron is located to determine the thermal neutron flux, neutron spectrum and dose equivalent. Furthermore, from a combination of measurements and Monte Carlo simulations the neutron source intensity at the target was estimated. The resulting intensity is in good agreement with the IAEA recommendations. Neutron doses derived from the measured spectra were found to vary between 7 and 320 mSv per 1 microA h of proton-integrated current. Finally, gamma doses were determined from TLD700 readings and amounted to around 10% of the neutron doses.