3-O-methyl-6-[18F]fluoro-L-DOPA and its evaluation in brain tumour imaging.

3-O-Methyl-6-[(18)F]fluoro-L-DOPA (OMFD) is a major metabolite of 6-[(18)F]fluoro-L-DOPA. Although synthesis of OFMD was primarily established to study the dopaminergic system, as it is an amino acid analogue, uptake in experimental tumours has been found. The aim of this study was to evaluate the applicability of OMFD for brain tumour imaging and to obtain initial estimates of whole-body biodistribution and radiation dosimetry in humans. Nineteen patients with suspected or confirmed brain tumours were investigated with OMFD and dynamic brain PET, complemented by whole-body PET in seven patients. Tracer kinetics were compared for normal brain and intracerebral lesions. Tissue accumulation was quantified with standardised uptake values (SUVs). Whole-body distribution in combination with tracer kinetics from animal experiments was used for the calculation of radiation dosimetry data. On the basis of OMFD PET, viable brain tumour was suspected in 16 patients with SUVs of 3.0+/-0.8 and a tumour to non-tumour ratio of 1.9+/-0.5. Highest tumour and normal brain uptake occurred between 15 and 30 min, with a subsequent slow decrease. Late whole-body tracer distribution was uniform without specific organ accumulation. Elimination occurred via urine. The mean radiation dose to the whole body was estimated at 0.016 mSv/MBq, with the kidneys as dose-critical organ (0.033 mGy/MBq). In conclusion, OMFD enables the visualisation of brain tumours with SUVs similar to other fluorinated amino acids. The whole-body radiation exposure from OMFD is comparable to that from FDG imaging.

18F-FDG for the staging of patients with differentiated thyroid cancer: comparison of a dual-head coincidence gamma camera with dedicated PET.

Coincidence imaging with a dual-head gamma camera may offer a cost-effective alternative to dedicated PET. The aim of this study was to compare the diagnostic accuracy of coincidence imaging and PET in patients with differentiated thyroid cancer. Thirty-one patients were studied after thyroidectomy and radioiodine ablation. They were injected with a single dose of 300 MBq 18F-FDG. Scanning was performed on a dedicated PET system after 1 hr, and on a coincidence gamma camera after 4 hrs. Based on a lesion-by-lesion comparison, coincidence imaging and PET concurred in 69% of 118 lesions. Based on lesion size, concurrence was 96% in lesions larger than 1.5 cm, and 62% in those between 1 and 1.5 cm. Lesions smaller than 1 cm could not be identified with coincidence imaging. Identical staging was obtained with coincidence imaging and PET in 26/31 patients (84%). In four patients FDG accumulating lesions were shown by both the coincidence camera and the dedicated scanner, but not detectable with any other imaging means and were confirmed histologically on surgery. Although a coincidence camera is technically inferior to a dedicated PET scanner, it may provide clinically useful results in situations were a lesion of sufficient size and FDG uptake is to be expected, e.g. when evaluating a known lesion for malignancy.

Significant reduction of the mass of bone metastasis 1 year after rhenium-186 HEDP pain palliation therapy.

A 59-year-old man with prostate cancer and pain from multiple bone metastases was treated with 1,424 MBq (38.5 mCi) rhenium-186 hydroxyethylidene diphosphonate (Re-186 HEDP). In addition, he had nonsteroidal antiandrogen, progestagen, and an analog-luteinizing hormone. Neither chemotherapy nor external-beam radiotherapy was administered. Bisphosponate therapy was stopped 4 weeks before the administration of Re-186 HEDP. The Tc-99m HMDP whole-body scan obtained 6 weeks after therapy showed the same results as before therapy. However, 1 year after therapy, a significant reduction of the mass of the metastases was visible on bone scan. The bone scan index decreased from 34 before therapy to 10 after 1 year. The patient described significant pain relief and stopped his analgesic intake 3 weeks after therapy.

[Comparison of rhenium-188, rhenium-186-HEDP and strontium-89 in palliation of painful bone metastases]. / Vergleich von Rhenium-188-HEDP, Rhenium-186-HEDP und Strontium-89 für die palliative Schmerztherapie von Skelettmetastasen.

AIM: Several radiopharmaceuticals were compared previously with regard to the efficiency in pain palliation of bone metastases. Furthermore, first results were reported on the suitability for such kind of therapy of the generator produced radionuclide rhenium-188. METHOD: Influence of Rhenium-188-HEDP (Re-188), Rhenium-186-HEDP (Re-186) and Strontium-89 (Sr-89) on pain symptoms and bone marrow function were obtained in 44 patients (pts). These were 16 pts. with Re-188 (2943 +/- 609 MBq), 13 pts. with Re-186 (1341 +/- 161 MBq) and 15 pts. with Sr-89 (152 +/- 18 MBq) (6 woman with breast cancer and 38 men with prostata cancer). RESULTS: 81 of pts. after Re-188, 77% after Re-186 and 80% after Sr-89 reported relief of pain. The Karnofsky-Index established by pts. increased from 74 +/- 9% to 85 +/- 11% after Re-188, from 70 +/- 11% to 76 +/- 11% after Re-186 and from 62 +/- 10% to 69 +/- 10% after Sr-89. However, the difference between the pre- and the post-therapeutic value is only statistically significant in the case of Re-188 therapy (p = 0.001). A decrease of platelets of 30 +/- 14% after 2.8 +/- 0.7 for pts. treated with Re-188, of 39 +/- 20% after 3.7 +/- 1.0 weeks for pts. treated with Re-186 and of 34 +/- 26% after 4.4 +/- 1.0 weeks for pts. treated with Sr-89 compared to the value before therapy was observed. The difference was not significant between the 3 groups of pts. (p = 0.125 to 0.862). CONCLUSION: All tried radiopharmaceuticals were effective in pain palliation. The various radionuclides had no significant difference in the pain relief or the bone marrow impairment. If only the Karnofsky-Index after Re-188 HEDP seems to be a little more increase.

Neuronavigation in surgery of intracranial and spinal tumors.

PURPOSE: To demonstrate the new possibilities and advantages of neuronavigation in the surgery of intracranial and spinal tumors, based on patient populations treated in our hospital. MATERIALS AND METHODS: An infrared navigation system with integrated microscope guidance was used for frameless intracranial neuronavigation. The biopsies of intracranial tumors were carried out using a frame-based stereotactic technique. Intracranial navigation was, in part, combined with the use of an intraoperative CT scanner and a three-dimensional ultrasound system for data acquisition, correction of brain shifts, and intraoperative quality control. The navigation was also supported by presurgical brain mapping with magnetic source imaging. Navigation in spinal surgery was exclusively performed using an infrared navigation system in combination with an intraoperative CT scanner. RESULTS: The stereotactic tumor biopsies (n = 57) were carried out with an accuracy of 91.4% as compared with the histological diagnosis. The work flow of stereotactic procedures could be increased by using the intraoperative CT scanner. Fifty-seven patients with intracranial tumors were treated with the aid of neuronavigation between July 1997 and December 1999. These patients showed an improvement from 80% to 86% on the Karnofsky index 8 weeks postoperatively. The majority of intracranial cases were primary brain tumors (n = 30) and metastases (n = 13) in functionally important areas of the brain. In four patients, a significant brain shift was observed during neuronavigation, and could be corrected by an image update using either the intraoperative CT scanner (n = 2) or the three-dimensional ultrasound system (n = 2). The presurgical brain mapping with magnetoencephalography was shown to be reliable in the sensory cortex (n = 25). Eleven patients with a thoracic or lumbar tumor were treated by open surgery or stabilization, using a combination of spinal neuronavigation and the intraoperative CT scanner. Two patients with spinal tumors underwent navigated biopsies. Neither of them showed a reduction in the clinical stage, but the Karnofsky index improved from 63% up to 72% 8 weeks postoperatively. CONCLUSION: Neuronavigation allows very precise intracranial and spinal surgery. The problem of brain shift during the navigation procedures has been solved by intraoperative image acquisition. The use of neuronavigation was shown to improve the postoperative quality of life of patients suffering from brain and spinal tumors.

Source localization and possible causes of interictal epileptic activity in tumor-associated epilepsy.

Electrophysiological studies in gliomas have demonstrated action potentials in neoplastic cells. These "spiking tumor cells" are, however, an enigma. In attempt to find evidences for spikes within tumoral borders, 21 patients with different intracerebral tumors were preoperatively screened for the occurrence of epileptogenic discharges using multichannel MEG and EEG. A correlation between histopathology and the distance between dipole and tumor border could be found. Glioma patients showed epileptic activities closer to the border than those with mixed glioneuronal neoplasms and metastases. Four glioma patients demonstrated epileptic activity within the tumor boundary, however, not in the deep center of the tumor. Patch-clamping of cells from acute glioma slices did not yield a correlation between the presence of voltage-gated sodium channels in tumor cells and the MEG/EEG data. Our results demonstrate that the zone with the highest epileptogenic potential is different in gliomas and other brain tumors. However, our data do not strongly suggest that glioma cells are directly involved in the generation of tumor-associated epilepsy in vivo via their capability to generate action potentials.

Rhenium-188-HEDP in the palliative treatment of bone metastases.

INTRODUCTION: Rhenium-188-HEDP (188Re-HEDP) is a new and attractive radiopharmaceutical for the treatment of bone pain due to metastases. As a product of a 188W/188Re generator it is convenient for clinical use. With a short physical half life of 16.9 hours and a maximal beta-energy of 2.1 MeV, it is suitable for therapy. METHODS: We investigated the influence of 188Re-HEDP on pain relief, analgesic intake and impairment of bone marrow function in 15 patients. All patients were interviewed using standardized questions before, and 1, 2, 3, 4, 8, and 12 weeks after therapy. Blood samples were drawn weekly for 12 weeks, and a blood count was performed. Patients underwent gamma camera imaging to determine the radionuclide accumulation 4, 20, and 28 hours after therapy. The patients were treated with 1600 to 3459 MBq of 188Re-HEDP. RESULTS: Patients showed an improvement of the Karnofsky performance index from 74 +/- 8% to 84 +/- 11% 12 weeks after therapy. This improvement was statistically significant (p = 0.001). Eighty percent of the patients described pain relief and reduction of analgesics. Twenty percent of the patients could discontinue their analgesics. Mean platelet count decreased from (284 +/- 84)*10(3)/microliter to (205 +/- 62)*10(3)/microliter, and mean leukocyte count from (7.5 +/- 1.5)*10(3)/microliter to (5.9 +/- 2.1)*10(3)/microliter after therapy. The maximal differences between the values of platelets and leukocytes before and after therapy were not statistically significant (p = 0.021 and p = 0.094). Prostate specific antigen decreased from 95 +/- 83 ng/ml to 41 +/- 21 ng/ml, the difference was not statistically significant (p = 0.443). The bone accumulation 4, 20, and 28 hours after therapy was 1.3 +/- 0.5%, 0.6 +/- 0.3%, and 0.45 +/- 0.2% of the injected dose of a single metastasis, and 57 +/- 17%, 15.5 +/- 2% and 11 +/- 3% in the whole body, respectively. The effective half-life of 188Re-HEDP was 15.3 +/- 3.0 hours in the bone metastases, and 11.4 +/- 2.8 hours in the whole body. This corresponds to a residence time of 0.22 +/- 0.25 hours in the bone metastases, and of 10.54 +/- 2.59 hours in the whole body. CONCLUSION: In a small patient population, 188Re-HEDP therapy for bone pain palliation was effective and was associated with minimal toxicity.

Incorporation of intraoperative computerized tomography in a newly developed spinal navigation technique.

OBJECTIVE: We report on the first successful incorporation of intraoperative computerized tomography in spinal navigation procedures. MATERIALS AND METHODS: All operations were performed with the aid of a Tomoscan M mobile CT system (Philips Medical Systems, Eindhoven, The Netherlands). The system comprises a mobile gantry, a mobile patient examination table, and a mobile workstation. Three different navigation systems were used: the EasyGuide (Philips Medical Systems, Eindhoven, The Netherlands), the Surgical Tool Navigator (Zeiss, Oberkochen, Germany), and a prototype of an ultrasound navigation system developed by ourselves (IVS GbR, Chemnitz, Germany). All surgical operations were performed with the patient positioned on the mobile table of the CT system. Following dorsal preparation of the vertebral region, the surgeon implanted small titanium screws in the vertebrae to serve as fiducial markers. Image data acquisition and image-to-patient registration were performed after implantation of the marker screws. The pedicle screws were inserted using the navigation system, and the position of each implant was confirmed by intraoperative CT scans. RESULTS: To date, 35 patients with various spine disorders have been operated upon using the technique described, and 161 pedicle screws have been inserted. There were no misplacements of pedicle screws. In three (1. 9 %) cases we observed lateral perforation (maximum 2 mm) of the lateral pedicle wall. We achieved a registration error of 0.85 mm (RMSE) +/- 0.42 mm (SD). CONCLUSIONS: The combination of intraoperative computerized tomography and spinal navigation allows easy navigation with a high application accuracy of 0.8 mm +/- 0.4 mm (SD) at the target point (measured in experiments with a plastic spine model). The possibility of performing an intraoperative quality check on demand markedly improves the safety of these procedures.

The nature of G-bands analyzed by chromosome stretching.

To investigate the nature of G-banding, chromosome stretching was performed on chromosome 6 at the 400-band level of normal human lymphocytes that had been cultivated and harvested using standard techniques. The GTG-banding patterns of five stretched chromosomes 6 were compared microscopically with each other and found to be identical at the 1,400-band level. A high-resolution ideogram at the 1,400-band level was constructed. The banding pattern at this level appeared to be very regular, with all dark bands at the 400-band level splitting into three to six dark subbands. While the dark subbands observed at the 1,400-band level seem to derive solely from the dark bands seen at the 400-band level, light bands visible at the 400-band level do not split into subbands, which is in contrast to the published (ISCN, 1995) ideograms. The splitting process, which was analyzed on the video monitor in more detail, shows that chromosome stretching is due mainly to the appearance of light subbands flanked by dark subbands. To shed more light on this phenomenon, the staining intensity of the dark bands and their subbands was measured while the chromosomes were stretched from the 400- to the 1,400-band level. At first, staining intensity was found to diminish in inverse proportion to the elongation of the chromosome, but then remained relatively unaffected until the dark subbands were gradually split up. After stretching to the 1,400-band level, these dark subbands were followed by newly appearing small light subbands, which were about the same size as the stretched light bands visible at the 400-band level. The results indicate that, in general, the light bands of human chromosomes are the preferentially stretched chromosome regions and that the resolution-dependent characteristic banding pattern of human chromosomes is mainly based on a fixed hierarchy of the stretchability of chromosomes.

The spreading of metaphases is a slow process which leads to a stretching of chromosomes.

In routine chromosome harvesting of blood lymphocytes it is well accepted that metaphase spreads are obtained from fixed mitotic cells which burst on the surface of slides during the dropping procedure. For confirmation and clarification, fixed mitotic cells were dropped onto coverslips and observed under an inverted microscope during the evaporation of the fixative. Fixed mitotic cells in the metaphase stage first stick onto the surface of the coverslip without changing their three-dimensional shape and they do not burst. Thereafter, when evaporation of the fixative occurs, they slowly flatten until they are spread. This slow process leads to a stretching of chromosomes which may be a prerequisite for high resolution banding patterns. Confocal laser scanning microscopic measurements of the length, thickness, and width of chromosomes after (i) short term evaporation of the fixative, (ii) evaporation of the fixative under routine harvesting conditions and (iii) a prolonged evaporation, confirmed the stretching of chromosomes. The humidity, the temperature, and the drying time of the fixative influence the dynamic flow of the remaining fixative on the slide. This dynamic flow leads to an intensive wash of the fixed mitotic cells with increasing concentrations of acetic acid which is primarily responsible for the better quality of the metaphase spread.

Parametric imaging in cerebral radionuclide angiography (RNA) by planar imaging improving presentation and objectivation of cerebral blood flow.

Methods of parametric imaging of radionuclide angiography using parameters like appearance time, peak time, transit time, height of peak, arterial slope and area of inflow were developed and evaluated regarding their diagnostic meaning in 111 patients suffering from TIA or PRIND and in 30 normal persons. The meaning of these single parameters could shown depended on the specificity of the diagnostic question. Local cerebral blood flow can be estimated most favourably by parametric images of area of inflow whereas transit time is most promising as a diagnostic tool for evaluation of total cerebral blood flow classified with reference to severity of the perfusion disturbance. Appearance time is suited very well to estimation of collateral perfusion. Blood flow in great cerebral arteries could be seen well by non parametric imaging of radioactivity inflow in the brain supplying arterial vessels in the cranial floor. Applying a combination of the parametric images, the sensitivity for detection of disturbances of cerebral blood flow amounts to 0.91. A specificity of 0.88 and accuracy of 0.90 were found. The described combination of evaluation of RNA using various parameters is considered a well suited method for detection of disturbances in local and total cerebral blood flow by means of planar imaging.

[Nuclear medicine functional diagnosis of the myocardium using (123) I-heptadecanoic acid]. / Nuklearmedizinische Funktionsdiagnostik des Myokards unter Anwendung von 123I-Heptadekansäure.

On the basis of the results which we obtained having performed 25 examinations on 15 patients with angina pectoris syndrome, myocardial infarctions and condition after bypass operation the preparation 123I hepatadecanoic acid produced in the Central Institute for Nuclear Research Rossendorf is very well suited for the scintigraphic demonstration of the myocardium. Moreover it is possible to recognize selectively diagnostically interesting regions with different radioactivity intake, retention and elimination of the radiopharmacon pharmacon and with the help of quantitative parameters to characterize concerning the metabolic efficiency. We consider the 123I hepatadecanoic acid suitable for the clinical use in establishing the global and regional metabolic efficiency of the myocardium. It is very well to be used for the primary diagnostics and represents an evident diagnostic remedy for the assessment of the course of myocardial diseases and the success of therapy.

[Myocardial scintigraphy using omega-I-123 heptadecanoic acid (Rossendorf) in patients with coronary disease]. / Die Myokardszintigraphie mit Omega-123I-Heptadekansäure (Rossendorf) bei Patienten mit koronarer Herzkrankheit.

Scintigraphy using labelled myocardial metabolism precursors makes possible a noninvasive qualitative--and increasingly also quantitative--evaluation of global and regional myocardium, both normally and insufficiently perfused, with normal and disturbed metabolism. Among the labelled precursors, free fatty acids appear as most important, especially the omega-123I-heptadecanoic acid. The experience with the use of this myocardial metabolism precursor in 23 examinations of 11 patients is described.

[Demonstration of dual liver systems after experimental auxiliary partial liver transplantation using the alternative of sequential hepatobiliary scintigraphy]. / Die hepatobiliäre Sequenzszintigraphie-Alternative zur Uberprüfung des Duallebersystems nach experimenteller auxiliärer Leberteiltransplantation.

Hepatobiliary sequential scintigraphies by 99m Tc-ROTOP-EHIDA were carried out for judging the dual liver system after experimental auxiliary transplantation of a part of the liver. A functional advantage of the host liver in contrast to the transplant was found in all cases investigated. Ischemic transplant damages could be detected in all experiments and were scintigraphically recognised at an early stage. In addition to transplants with a functioning entire parenchyma, the investigations showed transplants with functionally active parenchyma zones and such ones without any functional evidence. A quantifiable determination of the global functional capacity of the hepatobiliary system of both livers was possible and also the evidence on residual functions. The different behaviour of the kinetics of the radio-pharmacon with normal function and in case of hepatic ischemia is discussed.