Impact of the dosimetry approach on the resulting 90Y radioembolization planned absorbed doses based on 99mTc-MAA SPEC T-CT: is there agreement between dosimetry methods?

Background: Prior radioembolization, a simulation using 99mTc-macroaggregated albumin as 90Y-microspheres surrogate is performed. Gamma scintigraphy images (planar, SPECT, or SPECT-CT) are acquired to evaluate intrahepatic 90Y-microspheres distribution and detect possible extrahepatic and lung shunting. These images may be used for pre-treatment dosimetry evaluation to calculate the 90Y activity that would get an optimal tumor response while sparing healthy tissues. Several dosimetry methods are available, but there is still no consensus on the best methodology to calculate absorbed doses. The goal of this study was to retrospectively evaluate the impact of using different dosimetry approaches on the resulting 90Y-radioembolization pre-treatment absorbed dose evaluation based on 99mTc-MAA images. Methods: Absorbed doses within volumes of interest resulting from partition model (PM) and 3D voxel dosimetry methods (3D-VDM) (dose-point kernel convolution and local deposition method) were evaluated. Additionally, a new “Multi-tumor Partition Model” (MTPM) was developed. The differences among dosimetry approaches were evaluated in terms of mean absorbed dose and dose volume histograms within the volumes of interest. Results: Differences in mean absorbed dose among dosimetry methods are higher in tumor volumes than in non-tumoral ones. The differences between MTPM and both 3D-VDM were substantially lower than those observed between PM and any 3D-VDM. A poor correlation and concordance were found between PM and the other studied dosimetry approaches. DVH obtained from either 3D-VDM are pretty similar in both healthy liver and individual tumors. Although no relevant global differences, in terms of absorbed dose in Gy, between both 3D-VDM were found, important voxel-by-voxel differences have been observed. Conclusions: Significant differences among the studied dosimetry approaches for 90Y-radioembolization treatments exist. Differences do not yield a substantial impact in treatment planning for healthy tissue but they do for tumoral liver. An individual segmentation and evaluation of the tumors is essential. In patients with multiple tumors, the application of PM is not optimal and the 3D-VDM or the new MTPM are suggested instead. If a 3D-VDM method is not available, MTPM is the best option. Furthermore, both 3D-VDM approaches may be indistinctly used

Evaluation of spacial 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 18F-DOPA and 11C-(+)-α-dihydrotetrabenazine (11C-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, 18F-DOPA and 11C-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 11C-DTBZ PET. A symmetric reduction in striatal 11C-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

Autologous intramyocardial injection of cultured skeletal muscle-derived stem cells in patients with non-acute myocardial infarction

AIM: Experimental animal studies suggest that the use of skeletal myoblast in patients with myocardial infarction may result in improved cardiac function. The aim of the study was to assess the feasibility and safety of this therapy in patients with myocardial infarction. METHODS AND RESULTS: Twelve patients with old myocardial infarction and ischaemic coronary artery disease underwent treatment with coronary artery bypass surgery and intramyocardial injection of autologous skeletal myoblasts obtained from a muscle biopsy of vastus lateralis and cultured with autologous serum for 3 weeks. Global and regional cardiac function was assessed by 2D and ABD echocardiogram. 18F-FDG and 13N-ammonia PET studies were used to determine perfusion and viability. Left ventricular ejection fraction (LVEF) improved from 35.5+/-2.3% before surgery to 53.5+/-4.98% at 3 months (P=0.002). Echocardiography revealed a marked improvement in regional contractility in those cardiac segments treated with skeletal myoblast (wall motion score index 2.64+/-0.13 at baseline vs 1.64+/-0.16 at 3 months P=0.0001). Quantitative 18F-FDG PET studies showed a significant (P=0.012) increased in cardiac viability in the infarct zone 3 months after surgery. No statistically significant differences were found in 13N-ammonia PET studies. Skeletal myoblast implant was not associated with an increase in adverse events. No cardiac arrhythmias were detected during early follow-up. CONCLUSIONS: In patients with old myocardial infarction, treatment with skeletal myoblast in conjunction with coronary artery bypass is safe and feasible and is associated with an increased global and regional left ventricular function,improvement in the viability of cardiac tissue in the infarct area and no induction of arrhythmias

Statistical parametric maps of (18)F-FDG PET and 3-D autoradiography in the rat brain: a cross-validation study

PURPOSE: Although specific positron emission tomography (PET) scanners have been developed for small animals, spatial resolution remains one of the most critical technical limitations, particularly in the evaluation of the rodent brain. The purpose of the present study was to examine the reliability of voxel-based statistical analysis (Statistical Parametric Mapping, SPM) applied to (18)F-fluorodeoxyglucose (FDG) PET images of the rat brain, acquired on a small animal PET not specifically designed for rodents. The gold standard for the validation of the PET results was the autoradiography of the same animals acquired under the same physiological conditions, reconstructed as a 3-D volume and analysed using SPM. METHODS: Eleven rats were studied under two different conditions: conscious or under inhalatory anaesthesia during (18)F-FDG uptake. All animals were studied in vivo under both conditions in a dedicated small animal Philips MOSAIC PET scanner and magnetic resonance images were obtained for subsequent spatial processing. Then, rats were randomly assigned to a conscious or anaesthetized group for postmortem autoradiography, and slices from each animal were aligned and stacked to create a 3-D autoradiographic volume. Finally, differences in (18)F-FDG uptake between conscious and anaesthetized states were assessed from PET and autoradiography data by SPM analysis and results were compared. RESULTS: SPM results of PET and 3-D autoradiography are in good agreement and led to the detection of consistent cortical differences between the conscious and anaesthetized groups, particularly in the bilateral somatosensory cortices. However, SPM analysis of 3-D autoradiography also highlighted differences in the thalamus that were not detected with PET. CONCLUSION: This study demonstrates that any difference detected with SPM analysis of MOSAIC PET images of rat brain is detected also by the gold standard autoradiographic technique, confirming that this methodology provides reliable results, although partial volume effects might make it difficult to detect slight differences in small regions

Optimización de la dosimetría en la planificación de los tratamientos de radioembolización hepática con microesferas de 90Y

La radioembolización (RE) consiste en la administración por vía intraarterial hepática de microesferas marcadas con un isótopo radiactivo que emita radiación de corto alcance, que permita impartir dosis absorbidas elevadas en el tejido tumoral y limitar la dosis absorbida en el tejido sano. Su eficacia se basa en la vascularización característica del hígado y de los tumores hepáticos. El tejido hepático sano recibe su flujo sanguíneo a través de la vena porta, mientras que los tumores hepáticos se irrigan principalmente por la arteria hepática. El pequeño tamaño de las microesferas permite que lleguen hasta el tumor a través de la vasculatura hepática, quedando permanentemente implantadas dentro del sistema vascular tumoral e impidiendo su paso a la circulación venosa. La planificación de los tratamientos de RE, a partir de la imagen 99mTc-MAA SPECT-CT, es la única herramienta disponible que permite realizar una evaluación dosimétrica personalizada previa a la administración del tratamiento. El cálculo preciso de las dosis absorbidas favorece la optimización tanto de la selección de pacientes candidatos a RE como del proceso de planificación para maximizar su eficacia terapéutica y minimizar la toxicidad en tejido sano. Por tanto, una metodología dosimétrica optimizada y reproducible es no sólo importante, sino esencial. En la actualidad, prácticamente ninguno de los procesos que se engloban dentro de un procedimiento dosimétrico está completamente estandarizado. En este contexto, surge un gran interés en abordar la comparación de diferentes técnicas en una única serie de pacientes, que facilite la estandarización del uso de las mismas. El objetivo de este estudio de investigación es optimizar y estandarizar el procedimiento dosimétrico en la planificación de los tratamientos de RE hepática con 90Y-microesferas, cuantificando la repercusión de cada variante metodológica en la dosis absorbida ycaracterizando su impacto clínico. Se consideraron cuatro modelos dosimétricos diferentes, dos métodos multicompartimentales, el método de partición y el modelo de partición multitumor planteado como novedad en este trabajo, y dos métodos de dosimetría a nivel de vóxel. Se compararon las dosis absorbidas, tanto en el tejido sano como en el tejido tumoral, resultantes de aplicar estos modelos dosimétricos sobre las imágenes pre-tratamiento. Del análisis de los resultados obtenidos, se desprende que llevar a cabo una segmentación completa de los compartimentos, a partir de los contornos del hígado, el volumen diana y cada una de las lesiones individuales que constituyen el conglomerado tumoral, contribuye a que los cálculos dosimétricos sean más precisos, lo que permite optimizar la selección de pacientes candidatos a RE y aporta información importante para decidir el mejor esquema terapéutico para el paciente. Además, las metodologías empleadas para determinar parámetros como el índice TN y el factor de calibración han demostrado tener un impacto importante en el cálculo de las dosis absorbidas resultantes. Así, el procedimiento empleado tiene un papel fundamental en la dosimetría de los tratamientos de RE, y es esencial establecer una única metodología para su cálculo. El nuevo modelo de partición multi-tumor es una herramienta fácil de implementar y podría ser de gran utilidad en aquellos centros en los que no es posible implementar métodos de dosimetría a nivel de vóxel, ya que aporta una mayor precisión que el modelo de partición estándar en el cálculo de la dosis absorbida en el tejido tumoral. Como resultado final de este trabajo se diseñó un algoritmo de recomendaciones, cuyo principal objetivo es contribuir a la estandarización de los métodos empleados en la dosimetría pre-tratamiento. Así, en función de las herramientas disponibles y de los datos recogidos de cada paciente, cada centro puede elegir la forma de proceder más adecuada para el cálculo de las dosis absorbidas

Optimización de la dosimetría en la planificación de los tratamientos de radioembolización hepática con microesferas de 90Y

La radioembolización (RE) consiste en la administración por vía intraarterial hepática de microesferas marcadas con un isótopo radiactivo que emita radiación de corto alcance, que permita impartir dosis absorbidas elevadas en el tejido tumoral y limitar la dosis absorbida en el tejido sano. Su eficacia se basa en la vascularización característica del hígado y de los tumores hepáticos. El tejido hepático sano recibe su flujo sanguíneo a través de la vena porta, mientras que los tumores hepáticos se irrigan principalmente por la arteria hepática. El pequeño tamaño de las microesferas permite que lleguen hasta el tumor a través de la vasculatura hepática, quedando permanentemente implantadas dentro del sistema vascular tumoral e impidiendo su paso a la circulación venosa. La planificación de los tratamientos de RE, a partir de la imagen 99mTc-MAA SPECT-CT, es la única herramienta disponible que permite realizar una evaluación dosimétrica personalizada previa a la administración del tratamiento. El cálculo preciso de las dosis absorbidas favorece la optimización tanto de la selección de pacientes candidatos a RE como del proceso de planificación para maximizar su eficacia terapéutica y minimizar la toxicidad en tejido sano. Por tanto, una metodología dosimétrica optimizada y reproducible es no sólo importante, sino esencial. En la actualidad, prácticamente ninguno de los procesos que se engloban dentro de un procedimiento dosimétrico está completamente estandarizado. En este contexto, surge un gran interés en abordar la comparación de diferentes técnicas en una única serie de pacientes, que facilite la estandarización del uso de las mismas. El objetivo de este estudio de investigación es optimizar y estandarizar el procedimiento dosimétrico en la planificación de los tratamientos de RE hepática con 90Y-microesferas, cuantificando la repercusión de cada variante metodológica en la dosis absorbida ycaracterizando su impacto clínico. Se consideraron cuatro modelos dosimétricos diferentes, dos métodos multicompartimentales, el método de partición y el modelo de partición multitumor planteado como novedad en este trabajo, y dos métodos de dosimetría a nivel de vóxel. Se compararon las dosis absorbidas, tanto en el tejido sano como en el tejido tumoral, resultantes de aplicar estos modelos dosimétricos sobre las imágenes pre-tratamiento. Del análisis de los resultados obtenidos, se desprende que llevar a cabo una segmentación completa de los compartimentos, a partir de los contornos del hígado, el volumen diana y cada una de las lesiones individuales que constituyen el conglomerado tumoral, contribuye a que los cálculos dosimétricos sean más precisos, lo que permite optimizar la selección de pacientes candidatos a RE y aporta información importante para decidir el mejor esquema terapéutico para el paciente. Además, las metodologías empleadas para determinar parámetros como el índice TN y el factor de calibración han demostrado tener un impacto importante en el cálculo de las dosis absorbidas resultantes. Así, el procedimiento empleado tiene un papel fundamental en la dosimetría de los tratamientos de RE, y es esencial establecer una única metodología para su cálculo. El nuevo modelo de partición multi-tumor es una herramienta fácil de implementar y podría ser de gran utilidad en aquellos centros en los que no es posible implementar métodos de dosimetría a nivel de vóxel, ya que aporta una mayor precisión que el modelo de partición estándar en el cálculo de la dosis absorbida en el tejido tumoral. Como resultado final de este trabajo se diseñó un algoritmo de recomendaciones, cuyo principal objetivo es contribuir a la estandarización de los métodos empleados en la dosimetría pre-tratamiento. Así, en función de las herramientas disponibles y de los datos recogidos de cada paciente, cada centro puede elegir la forma de proceder más adecuada para el cálculo de las dosis absorbidas

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

Background: [F-18]-tetrafluoroborate is a PET radiotracer taken up by the sodium/iodide symporter (NIS). Albeit the in vivo behavior in rodents is similar to the (99)mTc-pertechnetate, no studies exist in primates or in humans. The aims of this study were to evaluate the biodistribution of [F-18]-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 [F-18]-tetrafluoroborate, prepared by isotopic exchange of sodium tetrafluoroborate with [F-18]-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: [F-18]-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: [F-18]-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 (99)mTc-pertechnetate but much lower than that produced by radioiodine in the form of (INa)-I-131, (INa)-I-123, or (INa)-I-124.MJO acknowledges support from the EPSRC (Life Sciences Interface Fellowship).S

Impact of the dosimetry approach on the resulting 90Y radioembolization planned absorbed doses based on 99mTc-MAA SPEC T-CT: is there agreement between dosimetry methods?

Background: Prior radioembolization, a simulation using 99mTc-macroaggregated albumin as 90Y-microspheres surrogate is performed. Gamma scintigraphy images (planar, SPECT, or SPECT-CT) are acquired to evaluate intrahepatic 90Y-microspheres distribution and detect possible extrahepatic and lung shunting. These images may be used for pre-treatment dosimetry evaluation to calculate the 90Y activity that would get an optimal tumor response while sparing healthy tissues. Several dosimetry methods are available, but there is still no consensus on the best methodology to calculate absorbed doses. The goal of this study was to retrospectively evaluate the impact of using different dosimetry approaches on the resulting 90Y-radioembolization pre-treatment absorbed dose evaluation based on 99mTc-MAA images. Methods: Absorbed doses within volumes of interest resulting from partition model (PM) and 3D voxel dosimetry methods (3D-VDM) (dose-point kernel convolution and local deposition method) were evaluated. Additionally, a new “Multi-tumor Partition Model” (MTPM) was developed. The differences among dosimetry approaches were evaluated in terms of mean absorbed dose and dose volume histograms within the volumes of interest. Results: Differences in mean absorbed dose among dosimetry methods are higher in tumor volumes than in non-tumoral ones. The differences between MTPM and both 3D-VDM were substantially lower than those observed between PM and any 3D-VDM. A poor correlation and concordance were found between PM and the other studied dosimetry approaches. DVH obtained from either 3D-VDM are pretty similar in both healthy liver and individual tumors. Although no relevant global differences, in terms of absorbed dose in Gy, between both 3D-VDM were found, important voxel-by-voxel differences have been observed. Conclusions: Significant differences among the studied dosimetry approaches for 90Y-radioembolization treatments exist. Differences do not yield a substantial impact in treatment planning for healthy tissue but they do for tumoral liver. An individual segmentation and evaluation of the tumors is essential. In patients with multiple tumors, the application of PM is not optimal and the 3D-VDM or the new MTPM are suggested instead. If a 3D-VDM method is not available, MTPM is the best option. Furthermore, both 3D-VDM approaches may be indistinctly used

Effective dose estimation for oncological and neurological PET/CT procedures

Background: The aim of this study was to retrospectively evaluate the patient effective dose (ED) for different PET/ CT procedures performed with a variety of PET radiopharmaceutical compounds. PET/CT studies of 210 patients were reviewed including Torso (n = 123), Whole body (WB) (n = 36), Head and Neck Tumor (HNT) (n = 10), and Brain (n = 41) protocols with 18FDG (n = 170), 11C-CHOL (n = 10), 18FDOPA (n = 10), 11C-MET (n = 10), and 18F-florbetapir (n = 10). ED was calculated using conversion factors applied to the radiotracer activity and to the CT dose-length product. Results: Total ED (mean ± SD) for Torso-11C-CHOL, Torso-18FDG, WB-18FDG, and HNT-18FDG protocols were 13.5 ± 2.2, 16.5 ± 4.5, 20.0 ± 5.6, and 15.4 ± 2.8 mSv, respectively, where CT represented 77, 62, 69, and 63% of the protocol ED, respectively. For 18FDG, 18FDOPA, 11C-MET, and 18F-florbetapir brain PET/CT studies, ED values (mean ± SD) were 6.4 ± 0.6, 4.6 ± 0.4, 5.2 ± 0.5, and 9.1 ± 0.4 mSv, respectively, and the corresponding CT contributions were 11, 14, 23, and 26%, respectively. In 18FDG PET/CT, variations in scan length and arm position produced significant differences in CT ED (p < 0.01). For dual-time-point imaging, the CT ED (mean ± SD) for the delayed scan was 3.8 ± 1.5 mSv. Conclusions: The mean ED for body and brain PET/CT protocols with different radiopharmaceuticals ranged between 4.6 and 20.0 mSv. The major contributor to total ED for body protocols is CT, whereas for brain studies, it is the PET radiopharmaceutical