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18F-FDG or 18F-FLT to detect transformation
PET
Each patient underwent a 18F-FDG as well as a 18F-FLT PET-CT within one week, in
random order, depending on logistics. After at least six hours of fasting, patients were
injected with ~ 185 MBq 18F-FDG or 18F-FLT iv. All studies were performed on a Gemini 2 TOF-64 PET-CT scanner (Philips Medical Systems, Best, The Netherlands). Low-dose
CT was collected using a beam current of 30 to 50 mAs at 120 keV. Images (3 minutes
per bed position) covered the mid-thigh to skull vertex trajectory, starting 60 minutes
post injection. Plasma glucose levels were routinely obtained before 18F-FDG PET-CT.
Calibration and scanning procedures complied with the EANM guidelines (17).
CT was reconstructed using an image matrix size of 512×512 resulting in voxel sizes of
1.17×1.17 mm and a slice thickness of 5 mm. For PET, data were reconstructed by means
of a raw action ordered subset expectation maximization algorithm using default
reconstruction parameters. Time of flight information was used during reconstruction.
Reconstructed images had an image matrix size of 144×144, a voxel size of 4×4 mm and
a slice thickness of 4 mm. The post reconstruction image resolution was 7 mm FWHM.
PET images were evaluated by two independent observers. Nodal 18F-FDG uptake
was classified as positive if uptake exceeded that of liver. 18F-FLT uptake was positive if
uptake was enhanced compared to local background.
18F-FDG and 18F-FLT uptake as defined with SUV (SUVmax, SUV A50%, SUV A70%)
were measured of all visually positive lymph nodes of at least 3cc (as defined with A50
VOI isocontouring, to account for partial volume effects) (18,19)
Tumor volumes of interest (VOI) were defined using a 3D region growing algorithm, as
described previously (20). This algorithm is based on the 3D search algorithm in the
IDL software package version 6.3 (Interactive Data Language, Research Systems Inc.,
Boulder, USA). In short, the program first searched for the location of the maximum voxel
value within a (semi-automatically or manually) predefined region. Next, using this
maximum value and its location as starting point, a 3D VOI was defined automatically
using a 3D region growing algorithm, including all voxels above a specified threshold.
This threshold was set at 50 and 70% of the sum of maximum and background values.
The local background value was derived automatically using a 3D shell of 1 voxel
thickness at 1.5 cm from the border of the initially estimated or (pre-)defined tumor
volume. This initial estimate is based on the 70% of maximum pixel value 3D isocontour
(21,22). SUVs were normalized to body weight and to serum glucose for 18F-FDG.
Since transformation in patients with FL might not occur in all lymph nodes
simultaneously, we hypothesized that the intrapatient variability of tracer uptake
might reflect the process of transformation. For either tracer, and for each patient,
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