Lilli Geworski

[18F]-FDG–PET in clinical stage I/II non-seminomatous germ cell tumours: results of the German multicentre trial

PURPOSE The aim of this study was to determine the predictive values of 2-[fluorine-18]fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) in primary staging in patients with newly diagnosed non-seminomatous germ cell tumour (NSGCT) clinical stage I/II. PATIENTS AND METHODS The hypothesis was that FDG-PET would improve the negative predictive value (NPV) from 70% to 90%, thus requiring a total of 169 patients. All scans underwent visual analysis by a reference team of nuclear medicine physicians. Results were validated by histology following retroperitoneal lymph node dissection. RESULTS Only 72 of the planned 169 patients were included, due to poor accrual. The prevalence of nodal involvement was 26%. Correct nodal staging by FDG-PET was achieved in 83% compared with correct computed tomography (CT) staging in 71%. CT had a sensitivity and specificity of 41% and 95%, respectively. Positive predictive value (PPV) and NPV were 87% and 67%, respectively. FDG-PET had a sensitivity and specificity of 66% and 98%, respectively. PPV was 95%. The primary end point was not reached, with an NPV of 78%. CONCLUSION FDG-PET as a primary staging tool for NSGCT yielded only slightly better results than CT. Both methods had a high specificity while false-negative findings were more frequent with CT. FDG-PET is mostly useful as a diagnostic tool in case of questionable CT scan.

Increased serotonin transporter availability in the brainstem of migraineurs

For decades, serotonin has been speculated to play a major role in migraine pathophysiology. The central serotonergic system is located in the raphe nuclei and the adjacent reticular formation in the brainstem. Recently, radioligands targeting the brain serotonin transport protein (SERT) have been developed. We used the highly specific SERT-radioligand 123I-ADAM [2-((2-((dimethylamino) methyl)phenyl)thio)-5-iodophenylamine] to test the hypothesis of the mesopontine serotonergic system being involved in the pathophysiology of migraine. Nineteen migraine patients and 10 healthy, age- and sex-matched controls were enrolled. The neuroimaging study was performed interictally during the pain-free interval. Single Photon Emission Computed Tomography (SPECT)-images were coregistered with MRI-scans. Region of interest (ROI)-analysis revealed a highly significant increase of 123I-ADAM uptake in the mesopontine brainstem of migraineurs (p < 0.001). In contrast, 123IADAM uptake in the thalamus did not differ significantly between migraineurs and controls. Our study demonstrates for the first time a significant increase of brainstem SERT-availability in migraineurs, suggesting a dysregulation of the brainstem serotonergic system. It remains to be elucidated whether the altered SERT-availability is causally related to migraine pathophysiology or whether it reflects secondary pathophysiological mechanisms.

Comparison of F-18 FET-PET with F-18 FDG-PET for biopsy planning of non-contrast-enhancing gliomas

Objective:The management of non-contrast-enhancing brain tumours largely depends on biopsy, which allows a differentiation of low-grade gliomas (LGG) from high-grade gliomas (HGG). The aim of this study was to compare positron emission tomography using 2-[18F]-fluoro-2-deoxy-d-glucose (FDG-PET) and O-(2-[18F]-fluoroethyl)-l-tyrosine (FET-PET) in terms of providing target regions for biopsies.Materials and methods:Fifteen consecutive patients with newly diagnosed brain tumours (n = 11) or suspected recurrence of a known LGG (n = 4), in whom MRI demonstrated no contrast enhancement, were studied by both FET-PET and FDG-PET. FET-PET, FDG-PET and MRI data were fused, and then transferred to the neurosurgical navigation system, prior to neurosurgical interventions.Results:Histology showed HGG (WHO grade III) in 6/15 and LGG (WHO grade II) in 9/15 patients. FET-PET revealed an increased intratumoural tracer uptake in 8/9 LGG and in 5/6 HGG. FDG-PET depicted hypermetabolic spots in 2/9 LGG and in 4/6 HGG. In 6 patients we observed an increased intratumoural uptake of both tracers. In 4 of them, the area of highest FET accumulation in the tumour corresponded to the focus of increased FDG uptake.Conclusions:FET-PET appears to be superior to FDG-PET for biopsy planning in non-contrast-enhancing brain tumours. FDG-PET does not provide any additional information in this issue.

Anti-leucine rich glioma inactivated 1 protein and anti-N-methyl-D-aspartate receptor encephalitis show distinct patterns of brain glucose metabolism in 18F-fluoro-2-deoxy-d-glucose positron emission tomography.

BackgroundPathogenic autoantibodies targeting the recently identified leucine rich glioma inactivated 1 protein and the subunit 1 of the N-methyl-D-aspartate receptor induce autoimmune encephalitis. A comparison of brain metabolic patterns in 18F-fluoro-2-deoxy-d-glucose positron emission tomography of anti-leucine rich glioma inactivated 1 protein and anti-N-methyl-D-aspartate receptor encephalitis patients has not been performed yet and shall be helpful in differentiating these two most common forms of autoimmune encephalitis.MethodsThe brain 18F-fluoro-2-deoxy-d-glucose uptake from whole-body positron emission tomography of six anti-N-methyl-D-aspartate receptor encephalitis patients and four patients with anti-leucine rich glioma inactivated 1 protein encephalitis admitted to Hannover Medical School between 2008 and 2012 was retrospectively analyzed and compared to matched controls.ResultsGroup analysis of anti-N-methyl-D-aspartate encephalitis patients demonstrated regionally limited hypermetabolism in frontotemporal areas contrasting an extensive hypometabolism in parietal lobes, whereas the anti-leucine rich glioma inactivated 1 protein syndrome was characterized by hypermetabolism in cerebellar, basal ganglia, occipital and precentral areas and minor frontomesial hypometabolism.ConclusionsThis retrospective 18F-fluoro-2-deoxy-d-glucose positron emission tomography study provides novel evidence for distinct brain metabolic patterns in patients with anti-leucine rich glioma inactivated 1 protein and anti-N-methyl-D-aspartate receptor encephalitis.

BETA RADIATION EXPOSURE OF STAFF DURING AND AFTER THERAPIES WITH 90Y-LABELLED SUBSTANCES

Radioimmunotherapies (RITs) and peptide receptor radiotherapies (PRRTs) with (90)Y-labelled compounds offer promising prospects for tumor treatment in nuclear medicine. However, when preparing and performing these therapies, which require manipulations of high activities of (90)Y (>1 GBq), technicians and physicians may receive high exposures, mainly to the skin of the hands. Even non-occupationally exposed persons, such as caregivers and family members, receive external exposures in the initial period after therapy, arising from the (90)Y in the patient. The local skin doses of the individual staff members, measured during RITs and PRRTs with thermoluminescence detectors fixed with tapes to the fingers, vary considerably. The exposure of staff can exceed the annual permissible dose limit of 500 mSv if radiation protection standards are low. Thus, adequate safety measures are needed. Measurements of the dose rate around patients, made using survey meters with sufficient response to beta particles, indicate that the exposure of caregivers and family members is considerably higher than previously assumed, and was dominated by primary beta radiation instead of bremsstrahlung. Nevertheless, under normal circumstances, the annual dose limits for the public (effective dose: 1 mSv, skin dose: 50 mSv) will be complied with.

Simultaneous dual-isotope solid-state detector SPECT for improved tracking of white blood cells in suspected endocarditis.

Aims High-energy resolution and sensitivity of novel cadmium-zinc-telluride (CZT) detector equipped SPECT systems facilitate simultaneous imaging of multiple isotopes and may enhance the detection of molecular/cellular signals. This may refine the detection of endocarditis. This study was designed to determine the feasibility and diagnostic accuracy of simultaneous imaging of inflammation with 111In-labeled white blood cells (WBCs) and myocardial perfusion with 99mTc-sestamibi, for localization of WBCs relative to the valve plane in suspected endocarditis. Methods and results A dedicated cardiac CZT camera (Discovery 530c, GE Healthcare) was employed. Anthropomorphic thorax phantom studies were followed by clinical studies in 34 patients with suspected infection of native valves (n = 12) or implants (n = 22). Simultaneous 111In-WBC/99mTc perfusion imaging was performed, and compared with standard 111In-WBC planar scintigraphy and SPECT-CT. Phantom studies ruled out significant radioisotope crosstalk. Downscatter on 99mTc images was not observed for 111In activity as high as 2.5*99mTc activity. In patients, image quality was superior for CZT imaging vs. conventional SPECT-CT and planar scintigraphy (P < 0.01). Cadmium-zinc-telluride dual isotope imaging improved reader confidence for detection of inflammatory foci. Diagnostic accuracy based on surgery or Duke Criteria during follow-up was highest for CZT imaging (P < 0.001). Conclusion Novel CZT SPECT technology improves the accuracy of molecular/cellular cardiac imaging. Simultaneous multi-isotope imaging with 111In and 99mTc is feasible and aids in the workup of suspected endocarditis.

The use of radiolabelled human serum albumin and SPECT/MRI co-registration to study inflammation in the cavernous sinus of cluster headache patients.

A sterile inflammation in the cavernous sinus was hypothesized to underlie cluster headache (CH). Neurogenic inflammation is accompanied by the extravasation of plasma proteins in the surrounding tissue. We tested the hypothesis of an inflammatory process in the cavernous sinus in CH patients using 99mTc-human serum albumin (HSA) and single photon emission computed tomography (SPECT). Six patients with episodic CH were enrolled. After baseline imaging, CH attacks were induced by IV injection of nitroglycerin. The patients remained untreated for 20 min. A second SPECT was performed after successful treatment. Region of interest (ROI) analysis was performed on the basis of coregistered MRI/SPECT data. There was no statistical difference between the 99mTc-HSA uptake in the ipsilateral cavernous sinus before and after induction of an acute CH attack. There was no evidence for 99mTc-HSA extravasation in the cavernous sinus during the active episode as compared with the remission phase. Our results do not support the hypothesis of an inflammation in the cavernous sinus.

Physical aspects of scintigraphy-based dosimetry for nuclear medicine therapy.

In 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.

Calibration Test of PET Scanners in a Multi-Centre Clinical Trial on Breast Cancer Therapy Monitoring Using 18F-FLT

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.

Radioembolisation mit 90Y-markierten Mikrosphären: Posttherapeutische Therapievalidierung mit Bremsstrahlungs-SPECT

During the last years angiographic Selective Internal Radiotherapy (SIRT) with (90)Y-labelled microspheres has become a common technique for the local-ablative treatment of cancer patients. SIRT is a palliative therapy concept for the treatment of liver malignancies. As a result of (90)Y-decay as β(-)-emitter without a concomitant gamma radiation, Bremsstrahlung imaging is needed to validate the distribution achieved by radioembolisation. This article demonstrates the method of imaging through phantom measurement and shows the advantages of post-therapeutic tomography by means of a patient study. Approaches for further optimization of Bremsstrahlung imaging are discussed.