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Molecular Radiation Therapy (MRT) is a valid therapeutic option for a wide range of malignancies, such as neuroendocrine tumors and liver cancers. In its practice, it is generally acknowledged that there is a need to evaluate the influence of different factors affecting the accuracy of dose estimates and to define the actions necessary to maintain treatment uncertainties at acceptable levels. The present study addresses the problem of uncertainty propagation in 90Y-PET quantification. We assessed the quantitative accuracy in reference conditions of three PET scanners (namely, Siemens Biograph mCT, Siemens Biograph mCT flow, and GE Discovery DST) available at three different Italian Nuclear Medicine centers. Specific aspects of uncertainty within the quantification chain have been addressed, including the uncertainty in the calibration procedure. A framework based on the Guide to the Expression of Uncertainty in Measurement (GUM) approach is proposed for modeling the uncertainty in the quantification processes, and ultimately, an estimation of the uncertainty achievable in clinical conditions is reported. [ABSTRACT FROM AUTHOR]

At a time of increasing evidence for dose-effect relationships in radioembolization (RE) with 90Y-microspheres, the general consensus is that there is an urgent need for accurate treatment planning and dose assessment in patients undergoing RE treatment. This work aimed at assessing the usefulness of 99mTc macroaggregated albumin (MAA) SPECT/CT imaging for personalized provisional RE dosimetry considering a 3D-printed patientlike phantom (AdboMan phantom). A homemade tool was developed in MATLAB for image analysis and absorbed dose calculation. Two dose calculaton methods were implemented and used to calculate dose volume histograms: (I) dose kernel method and (II) local energy deposition method. The accuracy of the two different dosimetric methods was evaluated by means of 3D γ -index (1%–1 mm and 2%–2 mm) implemented in the tool. Differences between the two dose calculation methods using the 3D γ -index are within 1%–1 mm and 2%–2 mm for all AbdoMan inserts, with a passing rate of 99.9% and 100%, respectively, proving a good agreement between the two calculation methods. The present study supports the use of 99mTc-MAA SPECT acquisition for provisional dosimetry along with the local energy deposition method to convert reconstructed SPECT data into absorbed dose maps. As long as 99mTc-MAA SPECT acquisitions are performed on liver lesions larger than 40 mm, the absorbed dose computed by means of the local energy deposition method can lead to results in line with those obtained by Monte Carlo calculations. [ABSTRACT FROM AUTHOR]

Radioembolization (RE) with 90Y-microspheres has gained widespread acceptance as a safe and effective technique for treating liver malignancies. Accurate quantification in RE is a key step in treatment planning optimization and is becoming a pressing issue in light of the Directive 2013/59/EURATOM. The aim of this study was to develop a SPECT/CT imaging protocol for quantitative imaging optimization in RE based on cutting edge imaging technology (Symbia IntevoTM system provided with the innovative xSPECT software) and a novel anthropomorphic 3D-printed phantom. In the present study, 99mTc-labeled macroaggregated albumin was used as a surrogate radiopharmaceutical for treatment planning. Gamma camera calibration factors and recovery coefficients were determined performing preliminary SPECT/CT acquisitions of a point source, a cylindrical homogeneous phantom and the NEMA/IEC phantom. Data reconstruction was performed using the built-in xSPECT package, using both the Ordered Subset Expectation–Maximization (OSEM) and the Ordered Subset Conjugated Gradient (OSCG) algorithm. Specific regions of interest (ROIs) were drawn on the MIM 6.1.7 system according to the physical volume. The quantification procedure was validated using the anthropomorphic phantom provided with a fillable liver section and spheres of different diameters (20 mm, 40 mm and a 40 mm spherical shell). The measured activity concentration in all geometries is consistent within 4%, demonstrating that the xSPECT software permit an absolute quantification in anthropomorphic geometry largely within the 10% recommended from the manufacturer. Caution is advised in the presence of spherical objects with a necrotic core, as underestimations in the order of 20% were obtained. [ABSTRACT FROM AUTHOR]

The Sorgentina-RF project will use fusion neutrons to produce 99Mo, a precursor of 99mTc, by irradiating natural molybdenum. 99Mo is produced by means of the inelastic reaction 100Mo(n, 2n)99Mo on 100Mo, which is an isotope of natural Mo. From a functional point of view, the project consists of two parts: an irradiation neutron source at 14 MeV and a radiochemistry facility dedicated to the extraction of 99Mo from the solid sample irradiated by the neutron source. Given the degree of complexity of such a facility, the risk management strategy is based on an integrated approach that combines the engineering method of safety with that of radiation protection. Therefore, design issues were studied and systems were planned according to both radiation protection and safety criteria already in the preliminary phase, allowing a general strengthening of the safety of the plant. This work discusses the preventive analysis and the related activities to identify the ways in which potential exposures to radiation may occur. In particular, the preliminary safety analysis is presented for the innovative rotating target, developed for the project, and, accordingly, some specific technical solutions are given to refine the initial design of the facility. [ABSTRACT FROM AUTHOR]

The therapeutic effect from molecular radiation therapy (MRT), on both tumour and normal tissue, is determined by the radiation absorbed dose. Recent research indicates that as a consequence of biological variation across patients the absorbed dose can vary, for the same administered activity, by as much as two orders of magnitude. The international collaborative EURAMET-EMRP project “Metrology for molecular radiotherapy (MetroMRT)” is addressing this problem. The overall aim of the project is to develop methods of calibrating and verifying clinical dosimetry in MRT. In the present paper an overview of the metrological issues in molecular radiotherapy is provided.

Abstract Background Cure rate of early Hodgkin Lymphoma are high and avoidance of late toxicities is of paramount importance. This comparative study aims to assess the normal tissue sparing capability of intensity-modulated radiation therapy (IMRT) versus standard three-dimensional conformal radiotherapy (3D-CRT) in terms of dose-volume parameters and normal tissue complication probability (NTCP) for different organs at risk in supradiaphragmatic Hodgkin Lymphoma (HL) patients. Methods Ten HL patients were actually treated with 3D-CRT and all treatments were then re-planned with IMRT. Dose-volume parameters for thyroid, oesophagus, heart, coronary arteries, lung, spinal cord and breast were evaluated. Dose-volume histograms generated by TPS were analyzed to predict the NTCP for the considered organs at risk, according to different endpoints. Results Regarding dose-volume parameters no statistically significant differences were recorded for heart and origin of coronary arteries. We recorded statistically significant lower V30 with IMRT for oesophagus (6.42 vs 0.33, p = 0.02) and lungs (4.7 vs 0.1 p = 0.014 for the left lung and 2.59 vs 0.1 p = 0.017 for the right lung) and lower V20 for spinal cord (17.8 vs 7.2 p = 0.02). Moreover the maximum dose to the spinal cord was lower with IMRT (30.2 vs 19.9, p Conclusions In HL male patients IMRT seems feasible and accurate while for women HL patients IMRT should be used with caution.

Abstract Background To assess the accuracy of fractionated stereotactic radiotherapy (FSRT) using a stereotactic mask fixation system. Patients and Methods Sixteen patients treated with FSRT were involved in the study. A commercial stereotactic mask fixation system (BrainLAB AG) was used for patient immobilization. Serial CT scans obtained before and during FSRT were used to assess the accuracy of patient immobilization by comparing the isocenter position. Daily portal imaging were acquired to establish day to day patient position variation. Displacement errors along the different directions were calculated as combination of systematic and random errors. Results The mean isocenter displacements based on localization and verification CT imaging were 0.1 mm (SD 0.3 mm) in the lateral direction, 0.1 mm (SD 0.4 mm) in the anteroposterior, and 0.3 mm (SD 0.4 mm) in craniocaudal direction. The mean 3D displacement was 0.5 mm (SD 0.4 mm), being maximum 1.4 mm. No significant differences were found during the treatment (P = 0.4). The overall isocenter displacement as calculated by 456 anterior and lateral portal images were 0.3 mm (SD 0.9 mm) in the mediolateral direction, -0.2 mm (SD 1 mm) in the anteroposterior direction, and 0.2 mm (SD 1.1 mm) in the craniocaudal direction. The largest displacement of 2.7 mm was seen in the cranio-caudal direction, with 95% of displacements < 2 mm in any direction. Conclusions The results indicate that the setup error of the presented mask system evaluated by CT verification scans and portal imaging are minimal. Reproducibility of the isocenter position is in the best range of positioning reproducibility reported for other stereotactic systems.

The aim of the present paper is twofold. Firstly, to assess the absorbed dose in small lesions using Monte Carlo calculations in a scenario of intratumoral injection of 90Y (e.g., percutaneous ablation). Secondly, to derive a practical analytical formula for the calculation of the absorbed dose that incorporates the absorbed fractions for 90Y. The absorbed dose per unit administered activity was assessed using Monte Carlo calculations in spheres of different size (diameter 0.5–20 cm). The spheres are representative of tumor regions and are assumed to be uniformly filled with 90Y. Monte Carlo results were compared with the macrodosimetric approach used for dose calculation in liver radioembolization. The results of this analysis indicate that the use of the analytic model provides dose overestimates below 10% for lesions with diameter larger than approximately 2 cm. However, for lesions smaller than 2 cm the analytic model is likely to deviate significantly (>10%) from Monte Carlo results, providing dose overestimations larger than 50% for lesions of 0.5 cm diameter. In this paper an analytical formula derived from MC calculations that incorporates the absorbed fractions for 90Y is proposed. In a scenario of intratumoral injection of microspheres, the proposed equation can be usefully employed in the treatment planning of spherical lesions of small size (down to 0.5 cm diameter) providing dose estimates in close agreement with Monte Carlo calculations (maximum deviation below 0.5%). [ABSTRACT FROM AUTHOR]

Background: PET/CT has recently been shown to be a viable alternative to traditional post-infusion imaging methods providing good quality images of Y-laden microspheres after selective internal radiation therapy (SIRT). In the present paper, first we assessed the quantitative accuracy of Y-PET using an anthropomorphic phantom provided with lungs, liver, spine, and a cylindrical homemade lesion located into the hepatic compartment. Then, we explored the accuracy of different computational approaches on dose calculation, including (I) direct Monte Carlo radiation transport using Raydose, (II) Kernel convolution using Philips Stratos, (III) local deposition algorithm, (IV) Monte Carlo technique (MCNP) considering a uniform activity distribution, and (V) MIRD (Medical Internal Radiation Dose) analytical approach. Finally, calculated absorbed doses were compared with those obtained performing measurements with LiF:Mg,Cu,P TLD chips in a liquid environment. Results: Our results indicate that despite Y-PET being likely to provide high-resolution images, the Y low branch ratio, along with other image-degrading factors, may produce non-uniform activity maps, even in the presence of uniform activity. A systematic underestimation of the recovered activity, both for the tumor insert and for the liver background, was found. This is particularly true if no partial volume correction is applied through recovery coefficients. All dose algorithms performed well, the worst case scenario providing an agreement between absorbed dose evaluations within 20%. Average absorbed doses determined with the local deposition method are in excellent agreement with those obtained using the MIRD and the kernel-convolution dose calculation approach. Finally, absorbed dose assessed with MC codes are in good agreement with those obtained using TLD in liquid solution, thus confirming the soundness of both calculation approaches. This is especially true for Raydose, which provided an absorbed dose value within 3% of the measured dose, well within the stated uncertainties. Conclusions: Patient-specific dosimetry is possible even in a scenario with low true coincidences and high random fraction, as in Y-PET imaging, granted that accurate absolute PET calibration is performed and acquisition times are sufficiently long. Despite Monte Carlo calculations seeming to outperform all dose estimation algorithms, our data provide a strong argument for encouraging the use of the local deposition algorithm for routine Y dosimetry based on PET/CT imaging, due to its simplicity of implementation. [ABSTRACT FROM AUTHOR]

The purpose of this study is to investigate the optimal reference geometry for gamma camera calibration. Yet another question of interest was to assess the influence of the number of 3D Ordered Subsets Expectation Maximization (3D-OSEM) updates on activity quantification for SPECT imaging with 177Lu. The accuracy of 177Lu activity quantification was assessed both in small and in large objects. Two different reference geometries, namely a cylindrical homogeneous phantom and a Jaszczak 16 ml sphere surrounded by cold water, were used to determine the gamma camera calibration factor of a commercial SPECT/CT system. Moreover, the noise level and the concentration recovery coefficient were evaluated as a function of the number of 3D-OSEM updates by using the SPECT/CT images of the reference geometry phantoms and those of a cold Jaszczak phantom with three hot spheres (16ml, 8ml and 4ml), respectively. The optimal choice of the number of 3D-OSEM updates was based on a compromise between the noise level achievable in the reconstructed SPECT images and the concentration recovery coefficients. The quantitative accuracy achievable was finally validated on a test phantom, where a spherical insert composed of two concentric spheres was used to simulate a lesion in a warm background. Our data confirm and extend previous observations. Using the calibration factor obtained with the cylindrical homogeneous phantom and the Jaszczak 16 ml sphere, the recovered activity in the test phantom was underestimated by -16.4% and -24.8%, respectively. Our work has led us to conclude that gamma camera calibration performed with large homogeneous phantom outperforms calibration executed with the Jaszczak 16ml sphere. Furthermore, the results obtained support the assumption that approximately 50 OSEM updates represent a good trade-off to reach convergence in small volumes, meanwhile minimizing the noise level. [ABSTRACT FROM AUTHOR]

A 54-year-old woman with metastatic colorectal carcinoma underwent liver radioembolization with (90)Y resin microspheres. Microsphere biodistribution was assessed 2 h after the treatment through a 20-min long (90)Y PET scan. Isodose map and lesion dose-volume histogram (DVH) were then evaluated using a MATLAB-based code. Response to therapy was assessed performing a (18)F-FDG PET 6 months after the treatment. At (90)Y PET the patient showed a well-defined horseshoe-shaped hepatic lesion with hot margins and a cold core. The lesion presented a heterogeneous DVH with a hot margin receiving an average radiation dose as high as 287 Gy and a cold area receiving an average radiation dose of 70 Gy approximately. Six months after the treatment the patient reported a complete remission of tumour areas which received a high radiation dose, while progression of metastases was observed in the area that presented scarce microsphere localization at (90)Y PET. According to our experience, the use of (90)Y PET voxel dosimetry may provide a useful tool to assess possible correlations between microsphere biodistribution and clinical outcome of the treatment. In agreement with current literature findings, an average radiation dose greater than approximately 100 Gy may be required to sterilize liver metastases. [ABSTRACT FROM AUTHOR]

A 54-year-old woman with metastatic colorectal carcinoma underwent liver radioembolization with Y resin microspheres. Microsphere biodistribution was assessed 2 h after the treatment through a 20-min long Y PET scan. Isodose map and lesion dose-volume histogram (DVH) were then evaluated using a MATLAB-based code. Response to therapy was assessed performing a F-FDG PET 6 months after the treatment. At Y PET the patient showed a well-defined horseshoe-shaped hepatic lesion with hot margins and a cold core. The lesion presented a heterogeneous DVH with a hot margin receiving an average radiation dose as high as 287 Gy and a cold area receiving an average radiation dose of 70 Gy approximately. Six months after the treatment the patient reported a complete remission of tumour areas which received a high radiation dose, while progression of metastases was observed in the area that presented scarce microsphere localization at Y PET. According to our experience, the use of Y PET voxel dosimetry may provide a useful tool to assess possible correlations between microsphere biodistribution and clinical outcome of the treatment. In agreement with current literature findings, an average radiation dose greater than approximately 100 Gy may be required to sterilize liver metastases. [ABSTRACT FROM AUTHOR]