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SummaryIn nuclear medicine therapy the treatment of tumours by radiation exposure from internally deposited labelled antibodies or labelled peptides is currently an active field of investigation. To permit the efficient delivery of high amounts of radiation dose to tumours while limiting the radiation dose to critical organs dosimetry calculations have to be performed. These are relying on scintigraphic data being input to the well known MIRD formalism.This paper focuses on the methods and the difficulties associated with the scintigraphic determination of organ kinetics. The physical properties of the well-known scintigraphic imaging modalities, PET, SPECT and planar scintigraphy, are discussed thereby taking into account the properties of the appropriate radionuclides currently being available for therapy and dosimetry. Several arguments are given and disputed for the limited clinical use of PET and SPECT in dosimetry and the ongoing preference of planar whole-body imaging as the method of choice. The quantitative restrictions still inherent to this method are also discussed in detail. Procedural recommendations are proposed covering all processes related to data acquisition, data correction and data analysis which finally lead to reliable estimations of organ dose.

Background The cannabinoid CB 1 receptor agonist Δ 9 -THC has been suggested for treatment of Tourette syndrome (TS). Based on animal studies, the CB 1 antagonist [ 123 I]AM281 (N-(Morpholin-4-yl)-1-(2,4-dichlorophenyl)-5-(4-[ 123 I]iodophenyl)-4-methyl-1H-pyrazole-3-carboxamide) has been proposed for single photon emission computed tomography (SPECT) in humans. Our aims were to 1) evaluate specific binding of [ 123 I]AM281 to CB 1 receptors in TS patients and 2) assess radiation exposure associated with the use of AM281 labeled with 123 I for SPECT and 124 I for positron emission tomography. Methods We employed [ 123 I]AM281 in six TS patients before and after Δ 9 -THC treatment. Dynamic SPECT, plasma measurements (including metabolite analysis with thin layer chromatography), and whole-body imaging were performed. Regions of interest derived from magnetic resonance images were used to extract from SPECT uptake in an area with high CB 1 density (lentiform nuclei) and reference regions. Specific over nonspecific partition coefficients V 3 ′′ were calculated. Whole-body images were carried out for dosimetric analysis. Data obtained with [ 123 I]AM281 were used to predict doses from [ 124 I]AM281. Results Mean V 3 ′′ ranged from .19 to .31 and did not change significantly after Δ 9 -THC treatment. Nevertheless, in the only patient with a marked clinical response, V 3 ′′ clearly declined. Thin layer chromatography revealed biexponential kinetics of tracer metabolism; about 60% remained nonmetabolized after 3 hours. Effective doses of .011 mSv/MBq for [ 123 I]AM281 and .34 for [ 124 I]AM281 were computed. Conclusions This study suggests that specific binding of [ 123 I]AM281 to CB 1 receptors can be detected in patients using SPECT. Radiation exposure with [ 123 I]AM281 is low; that with [ 124 I]AM281 is higher but acceptable for single investigations.

The aim of this study was to evaluate the cross-calibration of positron emission tomographs and their peripheral devices prior to a multicenter study. The instrumentation of 22 sites (including 24 dedicated PET scanners), including 21 that could be operated in 2D mode and 20 in 3D mode, was investigated according to standardized acquisition and reconstruction protocols, and the cross-calibration was checked against the dose calibrators (22 instruments) and the sample changer (20 instruments). The deviation of the cross-calibration to the dose calibrators was below 5% for 10 of 21 PET scanners (2D mode) and 6 of 20 (3D mode). For 6 (2D mode) and 6 (3D mode) scanners, the corresponding error was up to 10%. In turn, the deviation between dose calibrator and standard was less than 8% for 19 devices, and even less than 5% for 14 devices. In most of the well counters evaluated, the cross-calibration error was less than 10%. Although required in general, the cross-calibration between positron emission tomographs and their peripheral devices becomes even more critical when pooling data in the framework of quantitative clinical multicenter studies.

Quantitative determination of activity concentration has always been regarded as a goal of PET scanner design. Therefore, a linear response with respect to activity concentration is essential. To prove system linearity of response a test is proposed based on the determination of recovery coefficients (RC) for different object geometries. If all degrading effects, especially scatter and attenuation, are corrected to a sufficient degree of accuracy, the system behaves linearly resulting in a theoretical relationship between hot (HSRC) and cold spot recovery coefficients (CSRC). Therefore this relationship, applied to appropriate phantom data containing hot or cold spheres, combined with the constraints on asymptotic behaviour of RC can be used as a test of system linearity of response. After applying the system's standard corrections RC were determined using both 2D and 3D data acquisition modes. For both 2D and 3D data, HSRC directly measured showed an excellent agreement with the HSRC calculated from the CSRC. The analysis was extended to radionuclides of different positron ranges, to the effect of data smoothing, and to that of iterative reconstruction. The agreement between the RC determined under varying border conditions demonstrates the effectiveness of the corrections used in constituting system linearity. Therefore, the method proposed is used as a test of system linearity of response.

In emission tomography, the spread of regional tracer uptake to surrounding areas caused by limited spatial resolution of the tomograph must be taken into account when quantitating activity concentrations in vivo. Assuming linearity and stationarity, the relationship between imaged activity concentration and true activity concentration is only dependent on the geometric relationship between the limited spatial resolution of the tomograph in all three dimensions and the three-dimensional size and shape of the object. In particular it is independent of the type of object studied. This concept is characterized by the term "recovery coefficient". Recovery effects can be corrected for by recovery coefficients determined in a calibration measurement for lesions of simple geometrical shape. This method works on anatomical structures that can be approximated to simple geometrical objects. The aim of this study was to investigate whether recovery correction of appropriate structures is feasible in a clinical setting. Measurements were done on a positron emission tomography (PET) scanner in the 2D and 3D acquisition mode and on an analogue and digital single-photon emission tomography (SPET) system using commercially available software for image reconstruction and correction of absorption and scatter effects. The results of hot spot and cold spot phantom measurements were compared to validate the assumed conditions of linearity and stationarity. It can be concluded that a recovery correction is feasible for PET scanners down to lesions measuring about 1.5xFWHM in size, whereas with simple correction schemes, which are widely available, an object-independent recovery correction for SPET cannot be performed. This result can be attributed to imperfections in the commercially available methods for attenuation and scatter correction in SPET, which are only approximate.

International audience; UNLABELLED: A multi-centre trial using PET requires the analysis of images acquired on different systems We designed a multi-centre trial to estimate the value of 18F-FLT-PET to predict response to neoadjuvant chemotherapy in patients with newly diagnosed breast cancer. A calibration check of each PET-CT and of its peripheral devices was performed to evaluate the reliability of the results.MATERIAL AND METHODS: 11 centres were investigated. Dose calibrators were assessed by repeated measurements of a 68Ge certified source. The differences between the clocks associated with the dose calibrators and inherent to the PET systems were registered. The calibration of PET-CT was assessed with an homogeneous cylindrical phantom by comparing the activities per unit of volume calculated from the dose calibrator measurements with that measured on 15 Regions of Interest (ROIs) drawn on 15 consecutive slices of reconstructed filtered back-projection (FBP) images. Both repeatability of activity concentration based upon the 15 ROIs (ANOVA-test) and its accuracy were evaluated.RESULTS: There was no significant difference for dose calibrator measurements (median of difference -0.04%; min = -4.65%; max = +5.63%). Mismatches between the clocks were less than 2 min in all sites and thus did not require any correction, regarding the half life of 18F. For all the PET systems, ANOVA revealed no significant difference between the activity concentrations estimated from the 15 ROIs (median of difference -0.69%; min = -9.97%; max = +9.60%).CONCLUSION: No major difference between the 11 centres with respect to calibration and cross-calibration was observed. The reliability of our 18F-FLT multi-centre clinical trial was therefore confirmed from the physical point of view. This type of procedure may be useful for any clinical trial involving different PET systems.

SummaryIn 58 patients with Parkinsonism or dystonia striatal dopamine D2 receptors were investigated using 123l-iodobenzamide (123I-IBZM) single-photon emission computed tomography (SPECT). The influence of SPECT reconstruction methodology on semiquantification and the clinical value of 123I-IBZM SPECT were evaluated. Delineation of the striatal uptake and striatum/frontal cortex (ST/FC) ratios were improved by the use of compensation procedures for scatter and attenuation as well as the choice of an adequate filter. Satisfactory results were achieved using a Metz prefilter with a comparatively high order number (i. e. high cut-off and low suppression of higher frequencies via roll-off). Regarding clinical diagnoses it was not possible to differentiate between advanced idiopathic Parkinson’s disease (IP) and Parkinsonism of other aetiology (OP) on the basis of 123I-IBZM SPECT. But patients with IP and favourable response to L-Dopa showed significantly higher ST/FC ratios than those with fluctuating response. In patients with dystonia ST/FC ratios were significantly higher compared to patients with IP or OP.

A proposal is made for the test conditions to evaluate PET count rate performance. This performance depends in a complex manner on the spatial distribution of activity and scattering material. Therefore, a combined body phantom is proposed, which is as simple as possible but which adequately simulates the range of clinical application of a whole body tomograph. Taking into account the special properties of the new block detector design, a comprehensive test procedure is developed. This includes not only the common count rate characteristic, but also checks for the accuracy of randoms estimation and count loss correction schemes, and for the occurrence of pulse pile up. This is done for different source and scatter configurations, simulating brain, cardiac, and abdominal imaging, respectively. Examples are given, based on measurements of the latest generation PET scanners, namely the CT1 PT 931/08-12 and the Scanditronix PC 2048-07WB.

There are two competitive measuring techniques in emission tomography: SPECT and PET. The superiority of PET is founded not only on using physiological radionuclides and tracers such as carbon 11, oxygen 15, and nitrogen 13, but also on achieving a physical performance far in excess of that of SPECT. Considering the demands of cardiac studies, the performance of both methods is analyzed and compared and the inherent limitations are stated.