Heinz Hundeshagen

Dopamine transporter binding in Gilles de la Tourette syndrome

Abstract Preliminary studies in patients with Gilles de la Tourette syndrome (TS) provided evidence of presynaptic dopaminergic dysfunction, demonstrating increased reuptake sites. Therefore we investigated striatal dopamine transporter binding in 12 TS patients and 9 control subjects using single photon emission computed tomography and 123I-labeled 2β-carbomethoxy-3β-(4-iodophenyl)tropane. In TS patients we found significantly higher relative striatal activity ratios (mean ±SD 12.33±3.58) than in controls (9.36±1.35, P<0.05). Only five patients, however, showed straitum/occipital cortex ratios more than 2 SD above the normal means. Seven patients had activity ratios within the average ratio of the control group plus 2 SD. Regarding the relationship between clinical parameters and striatum/occipital cortex ratios, we found an association between binding ratios and “self-injurious behavior” and “lack of impulse control”. This study corroborates previous data suggesting an involvement of the dopaminergic system in TS pathology. Our results demonstrate that an increase in dopamine transporter capacity is a possible but not a necessary alteration, and which appears more likely when self-injurious behaviour and lack of impulse control are associated.

Evaluation of the incorporation of bone grafts used in maxillofacial surgery with [18F]fluoride ion and dynamic positron emission tomography

This study investigates the incorporation of bone grafts used in maxillofacial surgery by means of [18F]fluoride ion and positron emission tomography (PET). It considers patients who received pedicle grafts for mandibular reconstruction or onlay grafts for alveolar ridge augmentation. Dynamic PET images and arterialized venous blood samples were obtained within a 1-h period after i.v. injection of [18F-]fluoride. Assuming a three-compartment model and applying multilinear least squares fitting, bone blood flow (K1) and fluoride influx (Kmlf) were determined. Additionally Patlak plot analysis was used to calculate fluoride influx (Kpat). In cervical vertebral bodies as the reference region, mean values for flow ofK1 = 0.1162±0.0396 ml/min/ml and influx ofKmlf = 0.0508±0.0193 andKpat = 0.0385±0.0102 ml/min/ml were found. Essentially these figures are comparable with physiological values in animal and man reported in the literature. Early after surgery a significant increase in flow and influx compared to vertebral bodies was observed in the regions of osteosyntheses between grafts used for reconstruction and recipient bone (K1 = 0.2181,Kmlf = 0.1000 andKpat = 0.0666 ml/min/ml) and in onlay grafts (K1 = 0.2842,Kmlf = 0.1637 andKpat = 0.0827 ml/min/ml). At the same time pedicle grafts showed a significant increase in flow but not in influx (K1 = 0.2042,Kmlf = 0.0774 andKpat = 0.0529 ml/ min/ml). FurthermoreKpat was significantly lower in pedicle grafts than in onlay grafts. In follow-up studies a significant decrease in flow occurred in pedicle grafts and the regions of osteosyntheses. Moreover the latter showed a significant decrease inKmlf as well. It is concluded that [18F-] PET depicted increased blood flow and osteoblastic activity in onlay grafts and regions of osteosyntheses, indicating bone repair in the graft and adjacent host bone early after surgery. For the regions of osteosyntheses the decrease in both parameters corresponded to uncomplicated healing. The lack of increased influx, although flow was increased in pedicle grafts, most likely indicates that some necrosis occurred in these grafts despite patency of anastomoses. It may be concluded that [18F-] PET provides further insight into the biology of graft incorporation.

Bone scintigraphy in the evaluation of bone grafts used for mandibular reconstruction

Bone scintigraphy was applied in the follow-up of 24 patients who received bone grafts for reconstruction of the mandible after partial resection. Semiquantitative assessment of the grafts was done with a six-grade scoring system, based on comparison of tracer uptake in the graft and in the calvarium (as an internal control). Sixty-nine bone scans were evaluated. Late planar imaging was carried out in all cases, and single-photon emission tomography (SPET) was performed additionally in 34 of these cases. Complications were observed in four grafts. They occurred less frequently in revascularized grafts than in non-revascularized grafts. Planar scintigrams performed within 14 days after reconstruction showed a significantly higher tracer uptake in grafts with an uncomplicated further course than in those which developed complications. Follow-up scintigrams after 1 and 3 months revealed a significant increase in tracer uptake in grafts with an uncomplicated course. This was not apparent in grafts which developed complications. The tracer uptake was estimated to be higher on the basis of the SPET scans as compared with the planar scintigrams. It is concluded that bone scintigraphy is of prognostic value in the evaluation of bone grafts used for mandibular reconstruction. SPET seems to be more sensitive than planar imaging for the assessment of graft viability.

Non selective transport of [11C-methyl]-L-and D-methionine into a malignant glioma

Images obtained by X-ray CT, brain scintigraphy (99mTc-DTPA) and positron emission tomography (PET) with [11C-methyl]-L- and D-methionine in a case of malignant glioma are presented, showing good agreement of PET and CT findings, in particular nearly identical localization of L- and D-methionine accumulation, whereas the blood brain barrier is only slightly disturbed. In a greater number of patients the amount of accumulated stereoisomers do not differ on a significant level, indicating that a raised transport rate mediated by a carrier of low stereospecifity seems to contribute substantially to the increased uptake of [11C-methyl]-L-methionine in human brain tumors. Several cerebral functions and diseases have been studied with positron emission tomography (PET), which represents a clinical tool for visualizing metabolic activities rather than morphologic lesions (Reivich et al. 1985; Mazziotta et al. 1986). With regard to the malignancy of brain tumors DiChiro et al. (1982, 1984, 1985 a, b) showed a correlation between tumor grade and its glucose metabolism measured with 18F-fluorodeoxyglucose. An increased uptake of [11C-methyl]-L-methionine into tumor tissue has also been described (Hübner et al. 1980; Bergström et al. 1983; Kubota et al. 1984; Meyer et al. 1985; Schober et al. 1986b). Bustany et al. (1981, 1983, 1985a, b, 1986) developed a model for quantitative determination of protein synthesis, postulating that methionine incorporation into protein in brain tumors correlates with grade of malignancy. We do not believe that the uptake of [11C-methyl]-L-methionine mainly reflects protein synthesis, because [11C-methyl]-D-methionine is accumulated in normal brain tissue and intracranial tumors in nearly the same manner as [11C-methyl]-L-methionine, the physiological substrate for protein synthesizing enzymes (Meyer et al. 1985). The following case report illustrates these findings.

Uptake of 11C-L- and D-methionine in brain tumors

Abstract11C-labeled l-and d-methionine uptake was measured in seven patients with brain tumors using positron emission tomography. Tumors accumulated both isomers of the tracer. The strongest uptake occurred in tumors with a high grade of malignancy, while low grade tumors accumulated less activity. The l to d uptake ratio in tumor regions ranged from 0.92–1.25. Conventional 99mTc-DTPA scans revealed blood-brain barrier damage in two patients with no or only slight 11C-methionine accumulation, while one patient with a negative 99mTc-DTPA scan accumulated 11C-methionine in the tumor region. In view of the biochemical pathway of methionine and the present findings, it is concluded that the uptake reflects metabolic activity in brain tissue rather than uptake by diffusion due to disruption of the blood-brain barrier.

Specific Imaging of Dialysis-Related Amyloid Deposits Using 131I-Beta-2-Microglobulin

Dialysis-related amyloidosis (DRA), characterized by its association with beta 2-microglobulin (beta 2m), has become a major concern in long-term hemodialysis patients. Hitherto the diagnosis was based on histological examinations of tissue obtained by biopsy or during surgery. In this preliminary study a new noninvasive diagnostic method was developed using the affinity of beta 2m for its derived fibrils. 3 patients on long-term hemodialysis for 10-16 years with biopsy-proven DRA and 1 patient on chronic hemodialysis for only 6 months were examined after intravenous injection of 131I-labelled beta 2m. Specific local accumulation of radioactivity was noted in the DRA patients after 48 h, persisting for further 96 h and corresponding to clinically or radiologically evident sites of amyloid deposition and to several other hitherto unsuspected sites. Examination of an excised amyloid tumor subsequent to in vivo labelling confirmed a highly specific accumulation of radioactivity in the amyloid tissue but not in control tissue. In the patient on chronic hemodialysis for only 6 months, no specific local accumulation was detected even after 1 week. These findings provide in vivo evidence in man that a specific uptake of circulating amyloid precursor molecules into deposits occurs and that this uptake may be used to radiolabel even small tissue infiltrates of amyloid. This method therefore may not only allow an objective, noninvasive detection of DRA but may also be used to obtain new pathophysiologic insights into amyloid formation in man, as well as permitting the evaluation of preventive therapeutic strategies in prospective studies on new patients.

99mTc-diethyl-iodo-HIDA (JODIDA): a new hepatobiliary agent in clinical comparison with 99mTc-diisopropyl-HIDA (DISIDA) in jaundiced patients.

The new HIDA derivative, 99mTc-dimethyl-iodine-HIDA (JODIDA), was compared with 99mTc-diisopropyl-HIDA (DISIDA) in 17 patients with jaundice by means of paired cholescintigraphic imaging studies. The following parameters were visually assessed: the extent of urinary tract visualization, biliary contrast and appearance time, and gallbladder visualization and appearance time. In the 6 patients with a total bilirubin level of between 19 and 66 μmol/l (1.1 and 3.9 mg/dl), both radiopharmaceuticals gave similar results except for the moderate visualization of the urinary tract with DISIDA in contrast to JODIDA. In the remaining 11 patients with a total bilirubin level between 102 and 1303 μmol/l (6 and 76 mg/dl), JODIDA showed significant advantages over DISIDA: non-visualization of the urinary tract, stronger and faster biliary contrast, and better gallbladder visualization. JODIDA thus offered substantial diagnostic advantages over DISIDA in 8 of these patients. In 4 patients, the differential diagnosis of jaundice (intrahepatic or mechanical disorder) was possible with JODIDA, whereas DISIDA either could not visualize intestinal or gallbladder activity at all or could not differentiate it from the urinary tract. In one patients, JODIDA offered faster (18 h) diagnosis. In the remaining 3 patients, other, substantially false interpretations could be avoided through the use of JODIDA. Further clinical experience with JODIDA in more than 40 patients confirmed the results of this study. We concluded that JODIDA is of significant advantage over DISIDA in clinical situations such as total bilirubin level above 80–100 μmol/l (4.7 to 5.8 mg/dl), examination of small children and critically ill patients and suggestion of bile leakage. As there are also no clinical disadvantages, it could become the rediopharmaceutical of choice for hepatobiliary imaging.

Quantitative determination of regional extravascular lung water and regional blood volume in congestive heart failure

Regional extravascular lung water (rELW) and blood volume (rBV) in five controls and 14 patients with congestive heart failure (CHF) were measured by constant infusion of H215O and inhalation of 11CO using positron emission tomography (PET). The analysis of 18 regions per patient revealed a relatively homogenous level of rELW in the controls (x=0.11±0.02 g/cc; range, 0.08–0.21), whereas this increased in patients with CHF (0.17±0.02 g/cc; range, 0.10–0.51). The rBV was 0.21±0.02 g/cc in the controls and 0.17±0.02 g/cc in patients with CHF. A good correlation was found between the severity of chronic heart failure (according to the grading of the New York Heart Association) and mean extravascular lung water (ELW) (r=0.69), as well as between CHF and the ratio rELW/rBV (r=0.87); however, the correlation to hemodynamic data was less satisfactory (cardiac index, r=0.45; pulmonary capillary wedge pressure, r=0.47; ejection fraction, r=0.60). In supine controls, a progressive decrease in regional blood volume from the basal to the apical regions was observed, whereas the differences in ELW were only small. In patients with chronic heart failure, ELW in the basal parts was markedly increased, whereas in the apical regions, only minor deviations from the controls were observed. In the basal regions of these patients, the blood volume was reduced by about 30%. Instead of the normal basoapical gradient of blood volume, these patients showed a rather flat distribution. Radiographic findings of pulmonary edema generally appeared together with an ELW level of greater than 0.14 g/cc. We conclude that the amount and distribution of fluid in pulmonary congestion can be noninvasively assessed by PET.

Quantification of regional extravascular lung water in dogs with positron emission tomography, using constant infusion of 15O-labeled water

Continuous infusion of 15O-labeled water allows a quantitative measurement of the total water pool in the chest region by positron emission tomography (PET). By subsequent inhalation of 11CO the intravascular space (blood pool) can be quantitated as well. After a suitable normalization of the intravascular activities the extravascular water can be determined by subtraction of the blood pool from the water pool. The regional extravascular lung water distribution can be visualized in tomographic slices. The method was validated in an animal experiment using five dogs. They were measured before and after induction of a lung edema by IV injection of oleic acid. The increase of extravascular lung water was monitored by the thermodye-dilution method (TDD). The correlation of extravascular lung water as measured by TDD with PET measurements is good (r=0.94). The PET values agree also with gravimetric lung water determinations. An absolute quantitation of regional extravascular lung water is possible after absorption correction of the PET data via transmission measurements and calibration of the camera system. The uncertainty in the absolute quantification is±20%. In the experiments described here the mean extravascular lung water was 0.13 g/cm3 before and 0.25 g/cm3 after induction of lung edema.

Total body water, extracellular water, plasma volume, and total body potassium in cirrhosis of the liver

ZusammenfassungUntersucht wurden die Flüssigkeitsräume Extrazellulärwasser (82-Bromid; ECW), Ganzkörperwasser (3-THO; TBW), Intrazellulärwasser (ICW=TBW-ECW) und Plasmavolumen (51-Chrom; PV), sowie das Ganzkörperkalium (40-K; TBK) bei Lebercirrhotikern (n=12) im Vergleich zu einer Kontrollgruppe (n=12). Die auf das Körpergewicht bezogenen Größen ECW (39%), TBW (28%), ICW (19%) und PV (24%) fanden wir bei den an Lebercirrhose Erkrankten vergrößert, das Ganzkörperkalium (% des Sollwertes) um 28% erniedrigt. Diese Ergebnisse weisen darauf hin, daß bei der Lebercirrhose weniger die sogenannte fettfreie Substanz (lean body mass; LBM) als vielmehr die intrazelluläre Kaliumkonzentration verringert ist. (Cirrhose: 84±21 mol/l ICW; Kontrolle: 115±23 mmol/l ICW). Als Ursachen werden ein vermindertes Kalium (mmol) pro Zelle und eine vergrößerte intrazelluläre Wasserkonzentration (ml/kg) diskutiert. Die Korrelation zwischen dem TBK (%) und dem Serum-Kalium (mmol/l) beträgtr=0,56 (p<0,002). Die klinisch chemischen Parameter γ-Globuline, Cholinesterase, Serumnatrium und Albumine (g/l PV) korrelieren signifikant mit den charakteristischen Veränderungen der Flüssigkeitsräume und des Ganzkörperkaliums. Hierbei ist das auf das Körpergewicht bezogene Gesamtalbumin trotz der relativen Hypoalbuminämie nicht erniedrigt. Unsere Ergebnisse sprechen für die ‘overflow theory’ der Ascites-Pathogenese (Lieberman et al., 1970).SummaryExtracellular water (EWC; 82-bromide), total body water (TBW; 3-THO), intracellular water (ICW=TBW-ECW), plasma volume (PV; 51-Cr), and total body potassium (TBK; 40-K) were studied in patients with cirrhosis of the liver (n=12) and in controls (n=12). ECW (39%), TBW (28%), ICW (19%), and PV (24%) increased, TBK (28%) however, decreased in cirrhosis. The results indicate that it is less the lean body mass, but rather the intracellular potassium concentration that is lowered (cirrhosis: 84±21 mmol/l ICW; controls: 115±23 mmol/l ICW). Decreased potassium per cell (mmol) and increased intracellular water are discussed as possible reasons for this. The correlation between TBK (%) and serum potassium (mmol/l) was found to ber=0.56 (p<0.002). Correlations between the biochemical parameters gamma-globulins, cholin esterase, serum sodium and serum albumin (g/l PV) and characteristic fluid disturbances in cirrhosis are highly significant whereas albumin (g/kg bodyweight) was the same in both groups. We can support the ‘overflow theory’ of ascites formation [19].