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1.  Multiple window spatial registration error of a gamma camera: 133Ba point source as a replacement of the NEMA procedure 
The accuracy of multiple window spatial resolution characterises the performance of a gamma camera for dual isotope imaging. In the present study we investigate an alternative method to the standard NEMA procedure for measuring this performance parameter.
A long-lived 133Ba point source with gamma energies close to 67Ga and a single bore lead collimator were used to measure the multiple window spatial registration error. Calculation of the positions of the point source in the images used the NEMA algorithm. The results were validated against the values obtained by the standard NEMA procedure which uses a liquid 67Ga source with collimation.
Of the source-collimator configurations under investigation an optimum collimator geometry, consisting of a 5 mm thick lead disk with a diameter of 46 mm and a 5 mm central bore, was selected. The multiple window spatial registration errors obtained by the 133Ba method showed excellent reproducibility (standard deviation < 0.07 mm). The values were compared with the results from the NEMA procedure obtained at the same locations and showed small differences with a correlation coefficient of 0.51 (p < 0.05). In addition, the 133Ba point source method proved to be much easier to use. A Bland-Altman analysis showed that the 133Ba and the 67Ga Method can be used interchangeably.
The 133Ba point source method measures the multiple window spatial registration error with essentially the same accuracy as the NEMA-recommended procedure, but is easier and safer to use and has the potential to replace the current standard procedure.
PMCID: PMC2615416  PMID: 19068107
2.  Influence of increased target dose inhomogeneity on margins for breathing motion compensation in conformal stereotactic body radiotherapy 
Breathing motion should be considered for stereotactic body radiotherapy (SBRT) of lung tumors. Four-dimensional computer tomography (4D-CT) offers detailed information of tumor motion. The aim of this work is to evaluate the influence of inhomogeneous dose distributions in the presence of breathing induced target motion and to calculate margins for motion compensation.
Based on 4D-CT examinations, the probability density function of pulmonary tumors was generated for ten patients. The time-accumulated dose to the tumor was calculated using one-dimensional (1D) convolution simulations of a 'static' dose distribution and target probability density function (PDF). In analogy to stereotactic body radiotherapy (SBRT), different degrees of dose inhomogeneity were allowed in the target volume: minimum doses of 100% were prescribed to the edge of the target and maximum doses varied between 102% (P102) and 150% (P150). The dose loss due to breathing motion was quantified and margins were added until this loss was completely compensated.
With the time-weighted mean tumor position as the isocentre, a close correlation with a quadratic relationship between the standard deviation of the PDF and the margin size was observed. Increased dose inhomogeneity in the target volume required smaller margins for motion compensation: margins of 2.5 mm, 2.4 mm and 1.3 mm were sufficient for compensation of 11.5 mm motion range and standard deviation of 3.9 mm in P105, P125 and P150, respectively. This effect of smaller margins for increased dose inhomogeneity was observed for all patients. Optimal sparing of the organ-at-risk surrounding the target was achieved for dose prescriptions P105 to P118. The internal target volume concept over-compensated breathing motion with higher than planned doses to the target and increased doses to the surrounding normal tissue.
Treatment planning with inhomogeneous dose distributions in the target volume required smaller margins for compensation of breathing induced target motion with the consequence of lower doses to the surrounding organs-at-risk.
PMCID: PMC2637830  PMID: 19055768
3.  Metabolism of no-carrier-added 2-[18F]fluoro-L-tyrosine in rats 
Several fluorine-18 labelled fluoroamino acids have been evaluated as tracers for the quantitative assessment of cerebral protein synthesis in vivo by positron emission tomography (PET). Among these, 2-[18F]fluoro-L-tyrosine (2-[18F]Tyr) has been studied in mice at a low specific activity. Its incorporation into proteins is fast and metabolism via other pathways is limited. The present in vivo study was carried out in normal awake rats using no-carrier-added 2-[18F]Tyr. Under normal physiological conditions, we have studied the incorporation into proteins and the metabolism of the tracer in different brain areas.
No-carrier-added 2-[18F]Tyr was administered to awake rats equipped with chronic arterial and venous catheters. The time course of the plasma activity was studied by arterial blood sampling. The biodistribution of the activity in the main organs was studied at the end of the experiment. The distribution of radioactive species in plasma and brain regions was studied by acidic precipitation of the proteins and HPLC analysis of the supernatant.
The absolute uptake of radioactivity in brain regions was homogenous. In awake rats, no-carrier-added 2-[18F]Tyr exhibits a fast and almost quantitative incorporation into the proteins fractions of cerebellum and cortex. In striatum, this incorporation into proteins and the unchanged fraction of the tracer detected by HPLC could be lower than in other brain regions.
This study confirms the potential of 2-[18F]fluoro-L-tyrosine as a tracer for the assessment of the rate of protein synthesis by positron emission tomography. The observed metabolism suggests a need for a correction for the appearance of metabolites, at least in plasma.
PMCID: PMC2606674  PMID: 18990255
4.  NEOadjuvant therapy monitoring with PET and CT in Esophageal Cancer (NEOPEC-trial) 
Surgical resection is the preferred treatment of potentially curable esophageal cancer. To improve long term patient outcome, many institutes apply neoadjuvant chemoradiotherapy. In a large proportion of patients no response to chemoradiotherapy is achieved. These patients suffer from toxic and ineffective neoadjuvant treatment, while appropriate surgical therapy is delayed. For this reason a diagnostic test that allows for accurate prediction of tumor response early during chemoradiotherapy is of crucial importance. CT-scan and endoscopic ultrasound have limited accuracy in predicting histopathologic tumor response. Data suggest that metabolic changes in tumor tissue as measured by FDG-PET predict response better. This study aims to compare FDG-PET and CT-scan for the early prediction of non-response to preoperative chemoradiotherapy in patients with potentially curable esophageal cancer.
Prognostic accuracy study, embedded in a randomized multicenter Dutch trial comparing neoadjuvant chemoradiotherapy for 5 weeks followed by surgery versus surgery alone for esophageal cancer. This prognostic accuracy study is performed only in the neoadjuvant arm of the randomized trial. In 6 centers, 150 consecutive patients will be included over a 3 year period. FDG-PET and CT-scan will be performed before and 2 weeks after the start of the chemoradiotherapy. All patients complete the 5 weeks regimen of neoadjuvant chemoradiotherapy, regardless the test results. Pathological examination of the surgical resection specimen will be used as reference standard. Responders are defined as patients with < 10% viable residual tumor cells (Mandard-score).
Difference in accuracy (area under ROC curve) and negative predictive value between FDG-PET and CT-scan are primary endpoints. Furthermore, an economic evaluation will be performed, comparing survival and costs associated with the use of FDG-PET (or CT-scan) to predict tumor response with survival and costs of neoadjuvant chemoradiotherapy without prediction of response (reference strategy).
The NEOPEC-trial could be the first sufficiently powered study that helps justify implementation of FDG-PET for response-monitoring in patients with esophageal cancer in clinical practice.
Trial registration
PMCID: PMC3301128  PMID: 18671847
5.  A computerized Infusion Pump for control of tissue tracer concentration during Positron Emission Tomography in vivo Pharmacokinetic/Pharmacodynamic measurements 
A computer controlled infusion pump (UIPump) for regulation of target tissue concentration of radioactive compounds was developed for use in biological research and tracer development for PET.
Based on observed tissue or plasma kinetics after a bolus injection of the tracer an algorithm calculates the infusion needed to obtain a specified target kinetic curve. A computer feeds this infusion scheme into an infusion pump connected to an animal via a venous catheter. The concept was validated using [11C]Flumazenil administrated to Sprague-Dawley rats where the whole brain distribution and kinetic of the tracer was measured over time using a microPET-scanner. The accuracy and precision of the system was assessed by producing steady-state levels of the tracer and by mimicking kinetics after oral administration.
Various kinetic profiles could be generated, including rapid achievement of constant levels, or step-wise increased levels. The resulting tissue curves had low deviation from the target curves according to the specified criteria: AUC (%): 4.2 ± 2.8, Maximal deviation (%): 13.6 ± 5.0 and R2: 0.95 ± 0.02.
The UIPump-system is suitable for use in PET-research for assessment of PK/PD properties by simulation of different tracer tissue kinetics in vivo.
PMCID: PMC2430701  PMID: 18513382
6.  Perfusion scanning using 99mTc-HMPAO detects early cerebrovascular changes in the diabetic rat 
99mTc-HMPAO is a well-established isotope useful in the detection of regional cerebral blood flow. Diabetes gives rise to arterial atherosclerotic changes that can lead to significant end organ dysfunction, prominently affecting perfusion to the heart, kidneys, eyes and brain. In the current study, we investigated the role of 99mTc-HMPAO cerebral perfusion scans in detecting early vascular changes in the diabetic brain.
Cerebral perfusion studies were performed on both control and streptozotocin-(STZ) induced diabetic male Wistar rats. Rat brain imaging using a gamma camera was performed for each group 0.5, 2, 4, and 24 hours post 99mTc-HMPAO injection. Data processing for each cerebral perfusion scan was performed by drawing a region of interest (ROI) circumferentially around the brain (B). Background (BKG) due to signal from the soft tissue of each rat was subtracted. Brain 99mTc-HMPAO uptake minus background counts (net brain counts; NBC) were then compared between the two groups.
The NBC (mean ± SD) for the STZ group were statistically significantly higher (p = 0.0004) than those of the control group at each of the time points studied.
99mTc-HMPAO brain scan may be useful in the detection of early atherosclerotic changes in the diabetic rat brain.
PMCID: PMC2322850  PMID: 18559077

Results 1-6 (6)