GATE (Geant4 Application for Emission Tomography) is a Monte Carlo simulation platform developed by the OpenGATE collaboration since 2001 and first publicly released in 2004. Dedicated to the modelling of planar scintigraphy, single photon emission computed tomography (SPECT) and positron emission tomography (PET) acquisitions, this platform is widely used to assist PET and SPECT research. A recent extension of this platform, released by the OpenGATE collaboration as GATE V6, now also enables modelling of x-ray computed tomography and radiation therapy experiments. This paper presents an overview of the main additions and improvements implemented in GATE since the publication of the initial GATE paper (Jan et al 2004 Phys. Med. Biol. 49 4543-61). This includes new models available in GATE to simulate optical and hadronic processes, novelties in modelling tracer, organ or detector motion, new options for speeding up GATE simulations, examples illustrating the use of GATE V6 in radiotherapy applications and CT simulations, and preliminary results regarding the validation of GATE V6 for radiation therapy applications. Upon completion of extensive validation studies, GATE is expected to become a valuable tool for simulations involving both radiotherapy and imaging.

In lymphoid malignancies and in certain solid cancers such as medullary thyroid carcinoma, somewhat mixed success has been achieved when applying radioimmunotherapy (RIT) with beta-emitters for the treatment of refractory cases. The development of novel RIT with alpha-emitters has created new opportunities and theoretical advantages due to the high linear energy transfer (LET) and the short path length in biological tissue of alpha-particles. These physical properties offer the prospect of achieving selective tumoural cell killing. Thus, RIT with alpha-emitters appears particularly suited for the elimination of circulating single cells or cell clusters or for the treatment of micrometastases at an early stage. However, to avoid non-specific irradiation of healthy tissues, it is necessary to identify accessible tumoural targets easily and rapidly. For this purpose, a small number of alpha-emitters have been investigated, among which only a few have been used for in vivo preclinical studies. Another problem is the availability and cost of these radionuclides; for instance, the low cost and the development of a reliable actinium-225/bismuth-213 generator were probably determining elements in the choice of bismuth-213 in the only human trial of RIT with an alpha-emitter. This article reviews the literature concerning monoclonal antibodies radiolabelled with alpha-emitters that have been developed for possible RIT in cancer patients. The principal radio-immunoconjugates are considered, starting with physical and chemical properties of alpha-emitters, their mode of production, the possibilities and difficulties of labelling, in vitro studies and finally, when available, in vivo preclinical and clinical studies.

Liquid GE scintigraphy provided poor and unreliable information in terms of patient discrimination and the drawing of pathophysiological profiles of abnormal GE. Tlag and TRE may confirm GE alteration, especially when solid T1/2 values are at the superior limit of normality, and may improve the performance of GE scintigraphy, rather than using liquid parameters.

BackgroundDespite the early theoretical prediction of the 0+-0+ transition of 90Zr, 90Y-PET underwent only recently a growing interest for the development of imaging radioembolization of liver tumors. The aim of this work was to determine the minimum detectable activity (MDA) of 90Y by PET imaging and the impact of time-of-flight (TOF) reconstruction on detectability and quantitative accuracy according to the lesion size.MethodsThe study was conducted using a Siemens Biograph® mCT with a 22 cm large axial field of view. An IEC torso-shaped phantom containing five coplanar spheres was uniformly filled to achieve sphere-to-background ratios of 40:1. The phantom was imaged nine times in 14 days over 30 min. Sinograms were reconstructed with and without TOF information. A contrast-to-noise ratio (CNR) index was calculated using the Rose criterion, taking partial volume effects into account. The impact of reconstruction parameters on quantification accuracy, detectability, and spatial localization of the signal was investigated. Finally, six patients with hepatocellular carcinoma and four patients included in different 90Y-based radioimmunotherapy protocols were enrolled for the evaluation of the imaging parameters in a clinical situation.ResultsThe highest CNR was achieved with one iteration for both TOF and non-TOF reconstructions. The MDA, however, was found to be lower with TOF than with non-TOF reconstruction. There was no gain by adding TOF information in terms of CNR for concentrations higher than 2 to 3 MBq mL−1, except for infra-centimetric lesions. Recovered activity was highly underestimated when a single iteration or non-TOF reconstruction was used (10% to 150% less depending on the lesion size). The MDA was estimated at 1 MBq mL−1 for a TOF reconstruction and infra-centimetric lesions. Images from patients treated with microspheres were clinically relevant, unlike those of patients who received systemic injections of 90Y.ConclusionsOnly one iteration and TOF were necessary to achieve an MDA around 1 MBq mL−1 and the most accurate localization of lesions. For precise quantification, at least three iterations gave the best performance, using TOF reconstruction and keeping an MDA of roughly 1 MBq mL−1. One and three iterations were mandatory to prevent false positive results for quantitative analysis of clinical data.Trial registrationhttp://IDRCB 2011-A00043-38 P101103

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In tomographic medical imaging (PET, SPECT, CT), differences in data acquisition and organization are a major hurdle for the development of tomographic reconstruction software. The implementation of a given reconstruction algorithm is usually limited to a specific set of conditions, depending on the modality, the purpose of the study, the input data, or on the characteristics of the reconstruction algorithm itself. It causes restricted or limited use of algorithms, differences in implementation, code duplication, impractical code development, and difficulties for comparing different methods. This work attempts to address these issues by proposing a unified and generic code framework for formatting, processing and reconstructing acquired multi-modal and multi-dimensional data. The proposed iterative framework processes in the same way elements from list-mode (i.e. events) and histogrammed (i.e. sinogram or other bins) data sets. Each element is processed separately, which opens the way for highly parallel execution. A unique iterative algorithm engine makes use of generic core components corresponding to the main parts of the reconstruction process. Features that are specific to different modalities and algorithms are embedded into specific components inheriting from the generic abstract components. Temporal dimensions are taken into account in the core architecture. The framework is implemented in an open-source C++ parallel platform, called CASToR (customizable and advanced software for tomographic reconstruction). Performance assessments show that the time loss due to genericity remains acceptable, being one order of magnitude slower compared to a manufacturer's software optimized for computational efficiency for a given system geometry. Specific optimizations were made possible by the underlying data set organization and processing and allowed for an average speed-up factor ranging from 1.54 to 3.07 when compared to more conventional implementations. Using parallel programming, an almost linear speed-up increase (factor of 0.85 times number of cores) was obtained in a realistic clinical PET setting. In conclusion, the proposed framework offers a substantial flexibility for the integration of new reconstruction algorithms while maintaining computation efficiency.

PURPOSE 18F-Fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) is currently the standard technique to define minimal residual disease (MRD) status outside the bone marrow (BM) in patients with multiple myeloma (MM). This study aimed to define criteria for PET complete metabolic response after therapy, jointly analyzing a subgroup of newly diagnosed transplantation-eligible patients with MM enrolled in two independent European randomized phase III trials (IFM/DFCI2009 and EMN02/HO95). PATIENTS AND METHODS Two hundred twenty-eight patients were observed for a median of 62.9 months. By study design, PET/CT scans were performed at baseline and before starting maintenance (premaintenance [PM]). The five-point Deauville scale (DS) was applied to describe BM (BM score [BMS]) and focal lesion (FL; FL score [FS]) uptake and tested a posteriori in uni- and multivariable analyses for their impact on clinical outcomes. RESULTS At baseline, 78% of patients had FLs (11% extramedullary), 80% with an FS ≥ 4. All patients had BM diffuse uptake (35.5% with BMS ≥ 4). At PM, 31% of patients had visually detectable FLs (2% extramedullary), 24% and 67.7% of them with an FS of 3 and ≥ 4, respectively. At PM, 98% of patients retained residual BM diffuse uptake, which was significantly lower than at baseline (mainly between BMS 2 and 3, BMS was ≥ 4 in only 8.7% of patients). By both uni- and multivariable analysis, FS and BMS < 4 were associated with prolonged progression-free survival (PFS) and overall survival (OS) at PM (OS: hazard ratio [HR], 0.6 and 0.47, respectively; PFS: HR, 0.36 and 0.24, respectively) CONCLUSION FL and BM FDG uptake lower than the liver background after therapy was an independent predictor for improved PFS and OS and can be proposed as the standardized criterion of PET complete metabolic response, confirming the value of the DS for patients with MM.

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