Cerenkov and radioluminescence imaging of brain tumor specimens during neurosurgery

We presented the first example of Cerenkov luminescence imaging (CLI) and radioluminescence imaging (RLI) of human tumor specimens. A patient with a brain meningioma localized in the left parietal region was injected with 166 MBq of 90Y-DOTATOC the day before neurosurgery. The specimens of the tumor removed during surgery were imaged using both CLI and RLI using an optical imager prototype developed in our laboratory. The system is based on a cooled electron multiplied charge coupled device coupled with an f 150.95 17-mm C-mount lens. We showed for the first time the possibility of obtaining CLI and RLI images of fresh human brain tumor specimens removed during neurosurgery

Dosimetry optimization system and integrated software (DOSIS) : a comparison against Fluka code results over a standard phantom

Trabajo presentado en el X Latin American Symposium on Nuclear Physics and Applications (X LASNPA), 1-6 diciembre 2013. Montevideo, Uruguay.Actually, dual-imaging facilities allow obtainance of both mass and activity patient-specific distributions perfectly correlated, which are important to improve dose distributions estimations and radioimmunotherapy treatment planifications accuracy. Calculus methods at voxel level require both quantitative and qualitative validation to obtain improvements in patient-specific dosimetry. The present work presents advances on the development of a novel computational tool dedicated to 3D patient-specific dosimetry at voxel level; and its results analysis and visualization. With the aim of providing a dosimetric tool for planar and tridimensional methods at voxel level, as well as the development of a platform based on fullstochastic methods for α-, β- and γ-emitters used in radiopharmaceutical applications. DOSIS is based on the Boltzmann radiation transport equation to realize energy delivering calculations. Procedures for 2D and 3D dosimetry have been designed tacking into accont established formalism and standards on MIRD Pamphlets. Anatomic and metabolic images, and dose maps resulting of this calculus are analysed and procesed by a special developed and designed software. DOSIS has been preliminary validated on some standard clinic cases in comparison whith other standard procedures used commonly in radionuclide treatments, showing great accordance on its results and a friendly user usability. Finally, a dose calculation over a standard phantom is performed using DOSIS calculation code and FLUKA, validating the radiation transport code of DOSIS.publishedVersionFil: Pérez, Pedro Antonio. Universidad Nacional de Córdoba. Facultad de Matemática, Astronomía y Física; Argentina.Fil: Pérez, Pedro Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Física Enrique Gaviola; Argentina.Fil: Pérez, Pedro Antonio. Universidad Nacional de Córdoba. Laboratorio de Investigación e Instrumentación en Física Aplicada a la Medicina e Imágenes por Rayos X; Argentina.Fil: Pérez, Pedro Antonio. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas, Físico-Químicas y Naturales. Departamento de Física; Argentina.Fil: Botta, Francesca. European Institute of Oncology; Italia.Fil: Cremonesi, Marta. European Institute of Oncology; Italia.Fil: Ferrari, Mahila. European Institute of Oncology; Italia.Fil: Guerriero, Francesco. European Institute of Oncology; Italia.Fil: Malano, Francisco Mauricio. Universidad Nacional de Córdoba. Facultad de Matemática, Astronomía y Física; Argentina.Fil: Malano, Francisco Mauricio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Física Enrique Gaviola; Argentina.Fil: Malano, Francisco Mauricio. Universidad Nacional de Córdoba. Laboratorio de Investigación e Instrumentación en Física Aplicada a la Medicina e Imágenes por Rayos X; Argentina.Fil: Pedroli, Guido. European Institute of Oncology; Italia.Fil: Scarinci, Ignacio Emanuel. Universidad Nacional de Córdoba. Laboratorio de Investigación e Instrumentación en Física Aplicada a la Medicina e Imágenes por Rayos X; Argentina.Fil: Valente, Mauro Andrés. Universidad Nacional de Córdoba. Facultad de Matemática, Astronomía y Física; Argentina.Fil: Valente, Mauro Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Física Enrique Gaviola; Argentina.Fil: Valente, Mauro Andrés. Universidad Nacional de Córdoba. Laboratorio de Investigación e Instrumentación en Física Aplicada a la Medicina e Imágenes por Rayos X; Argentina.Física Atómica, Molecular y Química (física de átomos y moléculas incluyendo colisión, interacción con radiación, resonancia magnética, Moessbauer Efecto.

Methods for preparation and administration of lutetium-177 oxodotreotide 3.7 GBq: proceedings from an Italian advisory board

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Towards a Radio-guided Surgery with β−\beta^{-} Decays: Uptake of a somatostatin analogue (DOTATOC) in Meningioma and High Grade Glioma

A novel radio guided surgery (RGS) technique for cerebral tumors using $\beta^{-}$ radiation is being developed. Checking the availability of a radio-tracer that can deliver a $\beta^{-}$ emitter to the tumor is a fundamental step in the deployment of such technique. This paper reports a study of the uptake of 90Y labeled (DOTATOC) in the meningioma and the high grade glioma (HGG) and a feasibility study of the RGS technique in these cases.Comment: 21 pages, 5 figure

Impact of SPECT corrections on 3D-dosimetry for TARE

Purpose: Many centers aim to plan liver transarterial radioembolization (TARE) with dosimetry, even without CT-based attenuation correction (AC), or with unoptimized scatter correction (SC) methods. This work investigates the impact of presence vs absence of such corrections, and limited spatial resolution, on 3D dosimetry for TARE. Methods: Three voxelized phantoms were derived from CT images of real patients with different body sizes. Simulations of 99mTc-SPECT projections were performed with the SIMIND code, assuming three activity distributions in the liver: uniform, inside a "liver's segment," or distributing multiple uptaking nodules ("nonuniform liver"), with a tumoral liver/healthy parenchyma ratio of 5:1. Projection data were reconstructed by a commercial workstation, with OSEM protocol not specifically optimized for dosimetry (spatial resolution of 12.6 mm), with/without SC (optimized, or with parameters predefined by the manufacturer; dual energy window), and with/without AC. Activity in voxels was calculated by a relative calibration, assuming identical microspheres and 99mTc-SPECT counts spatial distribution. 3D dose distributions were calculated by convolution with 90Y voxel S-values, assuming permanent trapping of microspheres. Cumulative dose-volume histograms in lesions and healthy parenchyma from different reconstructions were compared with those obtained from the reference biodistribution (the "gold standard," GS), assessing differences for D95%, D70%, and D50% (i.e., minimum value of the absorbed dose to a percentage of the irradiated volume). γ tool analysis with tolerance of 3%/13 mm was used to evaluate the agreement between GS and simulated cases. The influence of deep-breathing was studied, blurring the reference biodistributions with a 3D anisotropic gaussian kernel, and performing the simulations once again. Results: Differences of the dosimetric indicators were noticeable in some cases, always negative for lesions and distributed around zero for parenchyma. Application of AC and SC reduced systematically the differences for lesions by 5%–14% for a liver segment, and by 7%–12% for a nonuniform liver. For parenchyma, the data trend was less clear, but the overall range of variability passed from −10%/40% for a liver segment, and −10%/20% for a nonuniform liver, to −13%/6% in both cases. Applying AC, SC with preset parameters gave similar results to optimized SC, as confirmed by γ tool analysis. Moreover, γ analysis confirmed that solely AC and SC are not sufficient to obtain accurate 3D dose distribution. With breathing, the accuracy worsened severely for all dosimetric indicators, above all for lesions: with AC and optimized SC, −38%/−13% in liver's segment, −61%/−40% in the nonuniform liver. For parenchyma, D50% resulted always less sensitive to breathing and sub-optimal correction methods (difference overall range: −7%/13%). Conclusions: Reconstruction protocol optimization, AC, SC, PVE and respiratory motion corrections should be implemented to obtain the best possible dosimetric accuracy. On the other side, thanks to the relative calibration, D50% inaccuracy for the healthy parenchyma from absence of AC was less than expected, while the optimization of SC was scarcely influent. The relative calibration therefore allows to perform TARE planning, basing on D50% for the healthy parenchyma, even without AC or with suboptimal corrections, rather than rely on nondosimetric methods

TestDose: A nuclear medicine software based on Monte Carlo modeling for generating gamma camera acquisitions and dosimetry

International audiencePURPOSE:The TestDose platform was developed to generate scintigraphic imaging protocols and associated dosimetry by Monte Carlo modeling. TestDose is part of a broader project (www.dositest.com) whose aim is to identify the biases induced by different clinical dosimetry protocols.METHODS:The TestDose software allows handling the whole pipeline from virtual patient generation to resulting planar and SPECT images and dosimetry calculations. The originality of their approach relies on the implementation of functional segmentation for the anthropomorphic model representing a virtual patient. Two anthropomorphic models are currently available: 4D XCAT and ICRP 110. A pharmacokinetic model describes the biodistribution of a given radiopharmaceutical in each defined compartment at various time-points. The Monte Carlo simulation toolkit gate offers the possibility to accurately simulate scintigraphic images and absorbed doses in volumes of interest. The TestDose platform relies on gate to reproduce precisely any imaging protocol and to provide reference dosimetry. For image generation, TestDose stores user's imaging requirements and generates automatically command files used as input for gate. Each compartment is simulated only once and the resulting output is weighted using pharmacokinetic data. Resulting compartment projections are aggregated to obtain the final image. For dosimetry computation, emission data are stored in the platform database and relevant gate input files are generated for the virtual patient model and associated pharmacokinetics.RESULTS:Two samples of software runs are given to demonstrate the potential of TestDose. A clinical imaging protocol for the Octreoscan™ therapeutical treatment was implemented using the 4D XCAT model. Whole-body "step and shoot" acquisitions at different times postinjection and one SPECT acquisition were generated within reasonable computation times. Based on the same Octreoscan™ kinetics, a dosimetry computation performed on the ICRP 110 model is also presented.CONCLUSIONS:The proposed platform offers a generic framework to implement any scintigraphic imaging protocols and voxel/organ-based dosimetry computation. Thanks to the modular nature of TestDose, other imaging modalities could be supported in the future such as positron emission tomography

Three-step radioimmunotherapy with yttrium-90 biotin: Dosimetry and pharmacokinetics in cancer patients

A three-step avidin-biotin approach has been applied as a pretargeting system in radioimmunotherapy (RIT) as an alternative to conventional RIT with directly labelled monoclonal antibodies (MoAbs). Although dosimetric and toxicity studies following conventional RIT have been reported, these aspects have not previously been evaluated in a three-step RIT protocol. This report presents the results of pharmacokinetic and dosimetric studies performed in 24 patients with different tumours. Special consideration was given to the dose delivered to the red marrow and to the haematological toxicity. The possible additive dose to red marrow due to the release of unbound yttrium-90 was investigated. The protocol consisted in the injection of biotinylated MoAbs (first step) followed 1 day later by the combined administration of avidin and streptavidin (second step). After 24 h, biotin radiolabelled with 1.85-2.97 GBq/m2 of 90Y was injected (third step). Two different chelating agents, DTPA and DOTA, coupled to biotin, were used in these studies, Indium-111 biotin was used as a tracer of 90Y to follow the biodistribution during therapy. Serial blood samples and complete urine collection were obtained over 3 days. Whole-body and single-photon emission tomography images were acquired at 1, 16, 24 and 40 h after injection. The sequence of images was used to extrapolate 90Y-biotin time-activity curves. Numerical fitting and compartmental modelling were used to calculate the residence time values (Ï ) for critical organs and tumour, and results were compared: the absorbed doses were estimated using the MIRDOSE3.1 software. The residence times obtained by the numerical and compartmental models showed no relevant differences (< 10%); the compartmental model seemed to be more appropriate, giving a more accurate representation of the exchange between organs. The mean value for the Ï in blood was 2.0 ± 1.1 h; the mean urinary excretion in the first 24 h was 82.5% ± 10.8%. Without considering any contribution of free 90Y, kidneys, liver, bladder and red marrow mean absorbed doses were 1.62 ± 1.14, 0.27 ± 0.23, 3.61 ± 0.70 and 0.11 ± 0.05 mGy/MBq, respectively; the effective dose was 0.32 ± 0.06 mSv/MBq, while the dose to the tumour ranged from 0.62 to 15.05 mGy/MBq. The amount of free 90Y released after the injection proved to be negligible in the case of 90Y-DOTA-biotin, but noteworthy in the case of 90Y-DTPA-biotin (mean value: 5.6% ± 2.5% of injected dose), giving an additive dose to red marrow of 0.18 ± 0.08 mGy per MBq of injected 90Y-DTPA-biotin. Small fractions of free 90Y originating from incomplete radiolabelling can contribute significantly to the red marrow dose (3.26 mGy per MBq of free 90Y) and may explain some of the high levels of haematological toxicity observed. These results indicate that pretargeted three-step RIT allows the administraton of high 90Y activities capable of delivering a high dose to the tumour and sparing red marrow and other normal organs. Although 90Y-biotin clears rapidly from circulation, the use of DOTA-biotin conjugate for a stable chelation of 90Y is strongly recommended, considering that small amounts of free 90Y contribute significantly in increasing the red marrow dose

Quantitative analysis of 90Y Bremsstrahlung SPECT-CT images for application to 3D patient-specific dosimetry

Aim: The aim of this study was to evaluate the accuracy of the activity quantification of single-photon emission computed tomography/computed tomography (SPECT-CT) 90Y-Bremsstrahlung images and to validate the S-voxel method. Methods: An anthropomorphic torso phantom with radioactive inserts (90Y) was acquired by SPECT-CT. Constant calibration factors (cps/MBq) for the quantification were evaluated, considering different volume, shape, position inside the phantom, activity concentration and background, and distance from detectors. S-voxel values (EGSnrc) were implemented in MATLAB R0086 USA software. Dose comparisons between S-voxel and the conventional Medical Internal Radiation Dose method were repeated in a group of 11 patients administered with 90Y-DOTATATE. Results: Using the appropriate calibration factors to recover the volume variability, the error about the measurement repeatability and the activity variation was within 4%. The variability of activity quantification, depending on the position in the phantom, detector distance, and background, was <10%, <5%, and <10%, respectively. The absorbed-dose values calculated by OLINDA were in agreement with the mean dose values obtained by the S-voxel method (difference, <10%). Conclusions: The results confirm that, with the hybrid SPECT-CT system, quantitative analysis of SPECT 90Y-Bremsstrahlung images and the generation of three-dmensional dose distributions are feasible. The improved analysis of Bremsstrahlung images could have a notable clinical impact, allowing to address the dosimetric verification to patients during the course of therapy. © Mary Ann Liebert, Inc. 2009

Dosimetry of 177 Lu-PSMA-617 after mannitol infusion and glutamate tablet administration: Preliminary results of EUDRACT/RSO 2016-002732-32 IRST protocol

Radio-ligand therapy (RLT) with 177 Lu-PSMA-617 is a promising option for patients with metastatic castration-resistant prostate-cancer (mCRPC). A prospective phase-II study (EUDRACT/RSO,2016-002732-32) on mCRPC is ongoing at IRST (Meldola, Italy). A total of 9 patients (median age: 68 y, range: 53–85) were enrolled for dosimetry evaluation of parotid glands (PGs), kidneys, red marrow (RM) and whole body (WB). Folic polyglutamate tablets were orally administered as PGs protectors and 500 mL of a 10% mannitol solution was intravenously infused to reduce kidney uptake. The whole body planar image (WBI) and blood samples were acquired at different times post infusion (1 h, 16–24 h, 36–48 h and 120 h). Dose calculation was performed with MIRD formalism (OLINDA/EXM software). The median effective half-life was 33.0 h (range: 25.6–60.7) for PGs, 31.4 h (12.2–80.6) for kidneys, 8.2 h (2.5–14.7) for RM and 40.1 h (31.6–79.7) for WB. The median doses were 0.48 mGy/MBq (range: 0.33–2.63) for PGs, 0.70 mGy/MBq (0.26–1.07) for kidneys, 0.044 mGy/MBq (0.023–0.067) for RM and 0.04 mGy/MBq (0.02–0.11) for WB. A comparison with previously published dosimetric data was performed and a significant difference was found for PGs while no significant difference was observed for the kidneys. For PGs, the possibility of reducing uptake by administering glutamate tablets during RLT seems feasible while further research is warranted for a more focused evaluation of the reduction in kidney uptake

The role of dosimetry in the high activity 90Y-ibritumomab tiuxetan regimens: Two cases of abnormal biodistribution

Radioimmunotherapy (RIT) with a commercially available brand of yttrium-90 (90Y)-ibritumomab-tiuxetan at the prescribed activity of 14.8 MBq/kg (0.4 mCi/kg) represents a complementary approach in the treatment of resistant/refractory B-cell non-Hodgkin's lymphoma. A trial based on higher activities is ongoing in our institute. In this paper, we report atypical pharmacokinetics and liver uptake in 2 patients. Before RIT, all patients underwent dosimetry with 111In-ibritumomab-tiuxetan. Imaging data were analyzed to obtain predicted absorbed doses to nontarget organs. Therapy was administered only if a 20-Gy-limit dose to normal organs (except red marrow) was guaranteed. Both patients we describe showed abnormal liver uptake, increasing for 6 days post injection. In patient 1, there was atypical biodistribution in whole-blood images at 16 hours, with a prevalent high liver uptake (45% at 20 hours). Injected activity (IA%) was above 40% at 26 hours in the liver and lower than 60% in the total body. In patient 2, early images showed regular biodistribution. Subsequent images showed progressive increase of liver uptake (above 25% of percent injected activity at 25 hours). Liver-absorbed doses of 51 and 53 Gy, respectively, would have resulted with the administration of the prescribed 56 MBq/kg. Following these dosimetric results, both patients did not receive the planned therapy. These findings support the recommendation to include dosimetry in high-dose RIT. © 2009 Copyright 2009, Mary Ann Liebert, Inc