Jörg Kotzerke

Whole-body 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) for accurate staging of Hodgkin's disease

BACKGROUND Staging of Hodgkins disease (HD) is accomplished by a variety of invasive and non-invasive modalities. This prospective study was undertaken to investigate the value of whole-body positron emission tomography (PET) with 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) in defining regions involved by lymphoma compared with conventional staging methods in patients with HD. PATIENTS AND METHODS Fourty-four newly diagnosed patients with HD underwent FDG-PET as part of their initial staging work-up. PET findings were correlated with findings of conventional staging including computed tomography, ultrasound, bone scanning, bone marrow biopsy, liver biopsy and laparotomy. When results of FDG-PET differed to those obtained by conventional methods reevaluation was performed by biopsy, if possible, or magnetic resonance imaging. RESULTS The results of FDG-PET were compared with three hundred twenty-one conventional staging procedures performed in 44 patients. FDG-PET was positive in 38 of 44 (86%) patients at sites of documented disease. PET detected additional lesions in five cases previously not identified by conventional staging methods. In another case a nodal lesion suspect on CT was negative at FDG-PET and was settled as true negative by biopsy. As a consequence of PET findings five patients had to be upstaged and one patient had to be downstaged, resulting in changes in treatment strategy in all six cases (14%). FDG-PET failed to visualize sites of HD in four patients. In two of our patients a false positive PET result was obtained. CONCLUSIONS Our data indicate that FDG-PET provides an imaging technique that appears to visualize involved lesions in most patients with HD and is useful in the management of these patients.

FDG uptake in breast cancer: correlation with biological and clinical prognostic parameters

Abstract. The aim of this study was to evaluate the possible correlation between preoperative FDG-PET results in human breast cancer and the prognostic markers Ki-67, c-erb B2, p53, oestrogen/progesterone receptor status, axillary lymph node status, tumour size and tumour grading. Seventy-five female patients with breast cancer were included in this prospective study. Patient selection was independent of tumour size and the suspected clinical stage of disease. A high-resolution full-ring scanner (Siemens ECAT HR+) was used for PET imaging. The FDG uptake of breast tumours was calculated as the tumour to background ratio (TBR). In resected cancer tissue specimens, the proliferative fraction was evaluated by Ki-67 immunostaining. Additionally, immunostaining of the prognostic markers c-erb B2, p53, and progesterone and oestrogen receptors was performed. Haematoxylin and eosin-stained sections were used for tumour grading. Correlations between FDG uptake and prognostic markers were assumed to be significant at P<0.05 using the Mann-Whitney U test. In ductal breast cancer, mean TBR was 17.3 (median 7.7, range 1.6–122.7), while in lobular cancer it was 6.5 (median 3.7, range 1.4–22.7). Mean proliferative fraction (% Ki-67 positive tumour cells) was 15%±13.8% (median 10%, range 0%–60%). Twenty-three carcinomas showed <5% Ki-67 positive tumour cells. Statistical analysis indicated a positive correlation between FDG uptake and proliferative index in ductal breast cancer (P<0.0001, r=0.63). By contrast, there was no correlation between FDG uptake and c-erb B2 (P=0.79), p53 (P=0.92), tumour grading (P=0.09), oestrogen receptor status (P=0.41), progesterone receptor status (P=0.34), axillary lymph node status (P=0.90) and tumour size (P=0.3). It is concluded that FDG uptake is significantly higher in ductal breast cancer than in lobular cancer (P<0.05). FDG uptake correlates with proliferative activity assessed by Ki-67 immunostaining (P<0.05). A significant correlation with the other prognostic markers, however, could not be demonstrated.

An accurate method for correction of head movement in PET

A method is presented to correct positron emission tomography (PET) data for head motion during data acquisition. The method is based on simultaneous acquisition of PET data in list mode and monitoring of the patients head movements with a motion tracking system. According to the measured head motion, the line of response (LOR) of each single detected PET event is spatially transformed, resulting in a spatially fully corrected data set. The basic algorithm for spatial transformation of LORs is based on a number of assumptions which can lead to spatial artifacts and quantitative inaccuracies in the resulting images. These deficiencies are discussed, demonstrated and methods for improvement are presented. Using different kinds of phantoms the validity and accuracy of the correction method is tested and its applicability to human studies is demonstrated as well.

Intracoronary β-Irradiation With a Liquid 188Re-Filled Balloon Six-Month Results From a Clinical Safety and Feasibility Study

Background—Coronary irradiation is a new concept to reduce restenosis. We evaluated the feasibility and safety of intracoronary irradiation with a balloon catheter filled with 188Re, a liquid, high-energy β-emitter. Methods and Results—Irradiation with 15 Gy at 0.5-mm tissue depth was performed in 28 lesions after balloon dilation (n=9) or stenting (n=19). Lesions included 19 de novo stenoses, 4 occlusions, and 5 restenoses. Irradiation time was 515±199 seconds in 1 to 4 fractions. There were no procedural complications. One patient died of noncardiac causes at day 23. One asymptomatic patient refused 6-month angiography. Quantitative angiography after intervention showed a reference diameter of 2.77±0.35 mm and a minimal lumen diameter of 2.36±0.43 mm. At 6-month follow-up, minimal lumen diameter was 1.45±0.88 mm (late loss index 0.57). Target lesion restenosis rate (>50% in diameter) was low (12%; 3 of 26). In addition, we observed 9 stenoses at the proximal or distal end of the irradiation zone, potent...

[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.

Beta-irradiation used for systemic radioimmunotherapy induces apoptosis and activates apoptosis pathways in leukaemia cells

Beta-irradiation used for systemic radioimmunotherapy (RIT) is a promising treatment approach for high-risk leukaemia and lymphoma. In bone marrow-selective radioimmunotherapy, beta-irradiation is applied using iodine-131, yttrium-90 or rhenium-188 labelled radioimmunoconjugates. However, the mechanisms by which beta-irradiation induces cell death are not understood at the molecular level. Here, we report that beta-irradiation induced apoptosis and activated apoptosis pathways in leukaemia cells depending on doses, time points and dose rates. After beta-irradiation, upregulation of CD95 ligand and CD95 receptor was detected and activation of caspases resulting in apoptosis was found. These effects were completely blocked by the broad-range caspase inhibitor zVAD-fmk. In addition, irradiation-mediated mitochondrial damage resulted in perturbation of mitochondrial membrane potential, caspase-9 activation and cytochrome c release. Bax, a death-promoting protein, was upregulated and Bcl-xL, a death-inhibiting protein, was downregulated. We also found higher apoptosis rates and earlier activation of apoptosis pathways after gamma-irradiation in comparison to beta-irradiation at the same dose rate. Furthermore, irradiation-resistant cells were cross-resistant to CD95 and CD95-resistant cells were cross-resistant to irradiation, indicating that CD95 and irradiation used, at least in part, identical effector pathways. These findings demonstrate that beta-irradiation induces apoptosis and activates apoptosis pathways in leukaemia cells using both mitochondrial and death receptor pathways. Understanding the timing, sequence and molecular pathways of beta-irradiation-mediated apoptosis may allow rational adjustment of chemo- and radiotherapeutic strategies.

Endovascular brachytherapy for the prevention of restenosis after angioplasty.

Abstract.Restenosis is an unsolved clinical and financial limitation of angioplasty. Local irradiation is a new approach for the reduction of restenosis. Several animal studies have demonstrated the effective inhibition of arterial neointimal proliferation by percutaneous or endovascular irradiation. High-dose-rate irradiation from gamma and beta sources can be applied from radioactive wires or seeds and from liquid beta-emitter-filled balloon catheters. Dosimetric calculations have been performed for all relevant radionuclides. An effective dose can be applied within 10 min to the treated arteries. Beta-emitters are characterized by a low tissue penetration, which simplifies radiation protection but complicates the achievement of a homogeneous dose distribution without centring of the irradiation source. Gamma-emitters are characterized by deep tissue penetration and delivery of almost the same dose to all vessel layers; however, considerable care with regard to radiation protection of the environment is required if gamma-emitters are used. The liquid-filled balloon ensures a homogeneous dose delivery due to the self-centring irradiation source but entails the possibility of radioactivity incorporation in the event of balloon rupture. The most attractive radionuclide for this purpose is rhenium-188, which is available from the 188W/188Re generator system. Radiation exposure after accidental incorporation can be limited by chelation with mercaptoacetyltriglycine or by subsequent oral administration of perchlorate. Initial clinical trials have demonstrated the feasibility of the various irradiation techniques and yielded encouraging results. The use of unsealed radioactivity in a balloon catheter involves the nuclear medicine physician in this new field of therapy. This review discusses the concepts, the radiotracers and the results of animal experiments and early clinical trials in the field of endovascular irradiation employed as a possible means to prevent restenosis after angioplasty.

Intracoronary β-irradiation with a rhenium-188-filled balloon catheter: a randomized trial in patients with de novo and restenotic lesions ☆

Background Restenosis requiring reintervention is the main limitation of coronary angioplasty. Intracoronary irradiation reduces neointimal proliferation. We studied the efficacy of a self‐centering liquid rhenium‐188‐filled balloon catheter for coronary &bgr;‐brachytherapy. Methods and Results After successful coronary angioplasty with or without stenting, 225 patients (71% de novo lesions) were randomly assigned to receive 22.5 Gy intravascular &bgr;‐irradiation in 0.5‐mm tissue depth (n=113) or to receive no additional intervention (n=112). Clinical and procedural data did not differ between the groups except a higher rate of stenting in the control group (63%) compared with the rhenium‐188 group (45%, P<0.02). After 6 months of follow‐up, late loss was significantly lower in the irradiated group compared with the control group, both of the target lesion (0.11±0.54 versus 0.69±0.81 mm, P<0.0001) and of the total segment (0.22±0.67 versus 0.70±0.82 mm, P<0.0001). This was also evident in the subgroup of patients with de novo lesions and independent from stenting. Binary restenosis rates were significantly lower at the target lesion (6.3% versus 27.5%, P<0.0001) and of the total segment (12.6% versus 28.6%, P<0.007) after rhenium‐188 brachytherapy compared with the control group. Target vessel revascularization rate was significantly lower in the rhenium‐188 (6.3%) compared with the control group (19.8%, P=0.006). Conclusions Intracoronary &bgr;‐brachytherapy with a rhenium‐188 liquid‐filled balloon is safe and efficiently reduces restenosis and revascularization rates after coronary angioplasty. (Circulation. 2003;107:3022‐3027.)

Automatische Volumenabgrenzung in der onkologischen PET – Bewertung eines entsprechenden Software-Werkzeugs und Vergleich mit manueller Abgrenzung anhand klinischer Datensätze

AIM Evaluation of a dedicated software tool for automatic delineation of 3D regions of interest in oncological PET. PATIENTS, METHODS The applied procedure encompasses segmentation of user-specified subvolumes within the tomographic data set into separate 3D ROIs, automatic background determination, and local adaptive thresholding of the background corrected data. Background correction and adaptive thresholding are combined in an iterative algorithm. Nine experienced observers used this algorithm for automatic delineation of a total of 37 ROIs in 14 patients. Additionally, the observers delineated the same ROIs also manually (using a freely chosen threshold for each ROI) and the results of automatic and manual ROI delineation were compared. RESULTS For the investigated 37 ROIs the manual delineation shows a strong interobserver variability of (26.8±6.3)% (range: 15% to 45%) while the corresponding value for automatic delineation is (1.1±1.0)% (range: <0.1% to 3.6%). The fractional deviation of the automatic volumes from the observer-averaged manual ones is (3.7±12.7)%. CONCLUSION The evaluated software provides results in very good agreement with observer-averaged manual evaluations, facilitates and accelerates the volumetric evaluation, eliminates the problem of interobserver variability and appears to be a useful tool for volumetric evaluation of oncological PET in clinical routine.

Automatic volume delineation in oncological PET

AIM Evaluation of a dedicated software tool for automatic delineation of 3D regions of interest in oncological PET. PATIENTS, METHODS The applied procedure encompasses segmentation of user-specified subvolumes within the tomographic data set into separate 3D ROIs, automatic background determination, and local adaptive thresholding of the background corrected data. Background correction and adaptive thresholding are combined in an iterative algorithm. Nine experienced observers used this algorithm for automatic delineation of a total of 37 ROIs in 14 patients. Additionally, the observers delineated the same ROIs also manually (using a freely chosen threshold for each ROI) and the results of automatic and manual ROI delineation were compared. RESULTS For the investigated 37 ROIs the manual delineation shows a strong interobserver variability of (26.8±6.3)% (range: 15% to 45%) while the corresponding value for automatic delineation is (1.1±1.0)% (range: <0.1% to 3.6%). The fractional deviation of the automatic volumes from the observer-averaged manual ones is (3.7±12.7)%. CONCLUSION The evaluated software provides results in very good agreement with observer-averaged manual evaluations, facilitates and accelerates the volumetric evaluation, eliminates the problem of interobserver variability and appears to be a useful tool for volumetric evaluation of oncological PET in clinical routine.