Monte Carlo simulation is an essential tool in emission tomography that can assist in the design of new medical imaging devices, the optimization of acquisition protocols and the development or assessment of image reconstruction algorithms and correction techniques. GATE, the Geant4 Application for Tomographic Emission, encapsulates the Geant4 libraries to achieve a modular, versatile, scripted simulation toolkit adapted to the field of nuclear medicine. In particular, GATE allows the description of time-dependent phenomena such as source or detector movement, and source decay kinetics. This feature makes it possible to simulate time curves under realistic acquisition conditions and to test dynamic reconstruction algorithms. This paper gives a detailed description of the design and development of GATE by the OpenGATE collaboration, whose continuing objective is to improve, document and validate GATE by simulating commercially available imaging systems for PET and SPECT. Large effort is also invested in the ability and the flexibility to model novel detection systems or systems still under design. A public release of GATE licensed under the GNU Lesser General Public License can be downloaded at http:/www-lphe.epfl.ch/GATE/. Two benchmarks developed for PET and SPECT to test the installation of GATE and to serve as a tutorial for the users are presented. Extensive validation of the GATE simulation platform has been started, comparing simulations and measurements on commercially available acquisition systems. References to those results are listed. The future prospects towards the gridification of GATE and its extension to other domains such as dosimetry are also discussed.

(11)C-Pittsburgh compound B (PiB) marks Abeta amyloidosis, a key pathogenetic process in Alzheimer disease (AD). The use of (11)C-PiB is limited to centers with a cyclotron. Development of the (18)F-labeled thioflavin derivative of PiB, (18)F-flutemetamol, could hugely increase the availability of this new technology. The aims of this phase 1 study were to perform brain kinetic modeling of (18)F-flutemetamol, optimize the image acquisition procedure, and compare methods of analysis (step 1) and to compare (18)F-flutemetamol brain retention in AD patients versus healthy controls in a proof-of-concept study (steps 1 and 2). In step 1, 3 AD patients (Mini-Mental State Examination, 22-24) and 3 elderly healthy controls were scanned dynamically during windows of 0-90, 150-180, and 220-250 min after injection of approximately 180 MBq of (18)F-flutemetamol, with arterial sampling. We compared different analysis methods (compartmental modeling, Logan graphical analysis, and standardized uptake value ratios) and determined the optimal acquisition window for step 2. In step 2, 5 AD patients (Mini-Mental State Examination, 20-26) and 5 elderly healthy controls were scanned from 80 to 170 min after injection. To determine overall efficacy, steps 1 and 2 were pooled and standardized uptake value ratios were calculated using cerebellar cortex as a reference region. No adverse events were reported. There was a strong correlation between uptake values obtained with the different analysis methods. From 80 min after injection onward, the ratio of neocortical to cerebellar uptake was maximal and only marginally affected by scan start time or duration. AD patients showed significantly increased standardized uptake value ratios in neocortical association zones and striatum, compared with healthy controls, whereas uptake in white matter, cerebellum, and pons did not differ between groups. Two AD patients were (18)F-flutemetamol-negative and 1 healthy control was (18)F-flutemetamol-positive. (18)F-flutemetamol uptake can be readily quantified. This phase 1 study warrants further studies to validate this (18)F-labeled derivative of PiB as a biomarker for Abeta amyloidosis.

We have characterized the biodistribution and dosimetry of ¹⁸F-3′-F-6-OH-BTA1 (¹⁸F-GE067), a newly developed radioligand to visualize and quantify amyloid burden, in healthy elderly human subjects. Methods: Six subjects (5 men and 1 woman; age range, 51–74 y) underwent dynamic whole-body PET/CT for 6 h after a bolus injection of ¹⁸F-GE067. Source organs were delineated on PET/CT. Individual organ doses and effective doses were determined. Results: No adverse events or clinically significant changes were observed. ¹⁸F-GE067 is excreted predominantly through the hepatobiliary system. The gallbladder, upper large intestine, and small intestine are the organs with the highest absorbed dose (average, 287, 173, and 155 μGy/MBq, respectively). The mean effective dose was 33.8 ± 3.4 μSv/MBq, a dose comparable to that of many other ¹⁸F-labeled radiopharmaceuticals. Conclusion: The estimated effective dose of ¹⁸F-GE067 for PET amyloid imaging was acceptable (class II-b defined by the World Health Organization), and relatively low variability between subjects was observed.

Geant4 application for tomographic emission (GATE) is a recently developed simulation platform based on Geant4, specifically designed for PET and SPECT studies. In this paper we present validation results of GATE based on the comparison of simulations against experimental data, acquired with a standard SPECT camera. The most important components of the scintillation camera were modelled. The photoelectric effect. Compton and Rayleigh scatter are included in the gamma transport process. Special attention was paid to the processes involved in the collimator: scatter, penetration and lead fluorescence. A LEHR and a MEGP collimator were modelled as closely as possible to their shape and dimensions. In the validation study, we compared the simulated and measured energy spectra of different isotopes: 99mTc, 22Na, 57Co and 67Ga. The sensitivity was evaluated by using sources at varying distances from the detector surface. Scatter component analysis was performed in different energy windows at different distances from the detector and for different attenuation geometries. Spatial resolution was evaluated using a 99mTc source at various distances. Overall results showed very good agreement between the acquisitions and the simulations. The clinical usefulness of GATE depends on its ability to use voxelized datasets. Therefore, a clinical extension was written so that digital patient data can be read in by the simulator as a source distribution or as an attenuating geometry. Following this validation we modelled two additional camera designs: the Beacon transmission device for attenuation correction and the Solstice scanner prototype with a rotating collimator. For the first setup a scatter analysis was performed and for the latter design. the simulated sensitivity results were compared against theoretical predictions. Both case studies demonstrated the flexibility and accuracy of GATE and exemplified its potential benefits in protocol optimization and in system design.