E Klemm’s research while affiliated with University of Bonn - Medical Center and other places

Whole-body fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging was performed during the follow-up of 33 patients suffering from differentiated thyroid cancer. Among them there were 26 patients with papillary and seven with follicular tumours. Primary tumour stage (pT) was pT1 in six cases, pT2 in eight cases, pT3 in three cases and pT4 in 14 cases. FDG PET was normal in 18 patients. In three patients a slightly increased metabolism was observed in the thyroid bed, assumed to be related to remnant tissue. In one case local recurrence, in ten cases lymph node metastases (one false-positive, caused by sarcoidosis) and in three cases distant metastases were found with FDG PET. In comparison with whole-body scintigraphy using iodine-131 (WBS) there were a lot of discrepancies in imaging results. Whereas three patients had distant metastases (proven with 131I) and a negative FDG PET, in four cases 131I-negative lymph node metastases were detectable with PET. Even in the patients with concordant "staging", differences between 131I and FDG were observed as to the exact lesion localization. Therefore, a coexistence of 131I-positive/FDG-negative, 131I-negative/FDG-positive and 131I-positive/FDG-positive malignant tissue can be assumed in these patients. A higher correlation of FDG PET was observed with hexakis (2-methoxyisobutylisonitrile) technetium-99m (I) (MIBI) scintigraphy (performed in 20 cases) than with WBS. In highly differentiated tumours 131I scintigraphy had a high sensitivity, whereas in poorly differentiated carcinomas FDG PET was superior. The clinical use of FDG PET can be recommended in all cases of suspected or proven recurrence and/or metastases of differentiated thyroid cancer and is particularly useful in cases with elevated serum thyroglobulin levels and negative WBS.

The purpose of this study was to compare the binding of various typical and atypical neuroleptics to striatal D2 dopamine receptors in schizophrenic patients. Fifty-six inpatients with schizophrenia, including 14 with schizoaffective disorder and one with schizophreniform disorder, were evaluated. Fourteen patients were neuroleptic free. Single photon emission computed tomography (SPECT) was performed 90 minutes after intravenous injection of [123I]benzamide ([123I]IBZM). Subsequent semiquantitative analysis of D2 receptor binding was done with the use of the basal ganglia (striatum)/frontal cortex (BG/FC) ratio of activity. Clinical symptoms were rated with the Positive and Negative Syndrome Scale and the Hamilton Depression Rating Scale. The BG/FC ratios in patients taking typical neuroleptics were significantly lower than those in the neuroleptic-free subjects but not lower than those in the patients taking atypical neuroleptics (clozapine, remoxipride). For atypical antipsychotics, a dose-dependent relationship with striatal D2 receptor binding could not be demonstrated. BG/FC ratios were not significantly correlated with clinical symptoms or with duration of illness. The results indicate that [123I]IBZM SPECT is useful for semiquantitative imaging of striatal D2 dopamine receptors and for estimating their blockade by neuroleptics. Thus, it may improve drug monitoring in psychiatric patients. Furthermore, the findings suggest a complex relationship between the antipsychotic effect of atypical neuroleptics and D2 receptor blockade.

Whole-body fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging was performed during the follow-up of 33 patients suffering from differentiated thyroid cancer. Among them there were 26 patients with papillary and seven with follicular tumours. Primary tumour stage (pT) was pT1 in six cases, pT2 in eight cases, pT3 in three cases and pT4 in 14 cases. FDG PET was normal in 18 patients. In three patients a slightly increased metabolism was observed in the thyroid bed, assumed to be related to remnant tissue. In one case local recurrence, in ten cases lymph node metastases (one false-positive, caused by sarcoidosis) and in three cases distant metastases were found with FDG PET. In comparison with whole-body scintigraphy using iodine-131 (WBS) there were a lot of discrepancies in imaging results. Whereas three patients had distant metastases (proven with131I) and a negative FDG PET, in four cases131I-negative lymph node metastases were detectable with PET. Even in the patients with concordant staging, differences between131I and FDG were observed as to the exact lesion localization. Therefore, a coexistence of131I-positive/FDG-negative,131I-negative/FDG-positive and131I-positive/FDG-positive malignant tissue can be assumed in these patients. A higher correlation of FDG PET was observed with hexakis (2-methoxyisobutylisonitrile) technetium-99m (I) (MIBI) scintigraphy (performed in 20 cases) than with WBS. In highly differentiated tumours131I scintigraphy had a high sensitivity, whereas in poorly differentiated carcinomas FDG PET was superior. The clinical use of FDG PET can be recommended in all cases of suspected or proven recurrence and/or metastases of differentiated thyroid cancer and is particularly useful in cases with elevated serum thyroglobulin levels and negative WBS.

Temporal lobe dysfunction has been postulated in affective disorders by different brain imaging techniques. To further elucidate the possible relationship between electrophysiological variables in rapid cycling mood disorders (RCMD) and temporal lobe dysfunction we firstly recorded sphenoidal EEGs in addition to surface EEGs and 99m Tc-HMPAO-SPECT in three patients with RCMD. As compared to surface recordings the sphenoidal electrodes record more specifically the electrical activity arising within the mesio-basal temporal lobe. The preliminary results indicate that there is a dysrhythmia and/or rhythmic delta activity in RCMD which was predominantly apparent in the left temporo-mesial region in two cases. Furthermore, there was a hypoperfusion in the left temporal and temporo-parietal region using 99m Tc-HMPAO-SPECT technique in two patients, respectively. This pilot study suggests that temporal lobe structures might be of particular relevance in RCMD and thus provides further evidence suggestive of temporal lobe involvement in affective disorders. Our findings indicate that electrophysiological recordings and brain imaging techniques could be helpful in further elucidating the pathophysiology underlying rapid cycling mood disorders.

The striatal dopamine-D2-receptor uptake of 123I-IBZM in 32 patients (18 without and 14 under therapy with typical neuroleptics) was measured semiquantitatively using different ROI techniques. The aim of the study was to evaluate the influence of these techniques on the different ratios (striatum/cortex) found by various examiners. Using the same SPECT system no major differences were found between rectangular and manually drawn ROIs of the same size. All ROI techniques could differentiate between patients with and without therapy on a highly significant level. Therefore, the resulting ratio is mainly dependent on the spatial resolution of the camera system and only to a relatively minor extent on the ROI technique. Ratios obtained by different observers are not comparable quantitatively.

The aim of the present study was to see whether HMPAO-SPECT may contribute to the differentiation between dementia of the Alzheimer type (DAT) and major depression (MD). The results in 77 patients with memory impairment were evaluated. 48 patients suffered from DAT and 29 from MD. Initially, the defects in SPECT imaging were attributed to a cerebral region and the degree of decrease was evaluated (-1/-2/-3). Thereafter, the results were classified by 7 categories. In some of these categories an accumulation of cases of either DAT or MD was found. 35% of the patients suffering from DAT had bilateral defects with distinct (> -1) parietal/parietotemporal hypoperfusions, but no patient with MD showed this perfusion pattern. 62% of the patients with MD had unilateral defects but only 31% of the patients with DAT. The present study demonstrates that only 35% of all patients suffering from DAT show a perfusion pattern, thought earlier as "pathognomonic" for this disease. This perfusion pattern--if it exists--may be used as a safe criterion to exclude MD. Beyond that no clearcut ("specific") perfusion pattern may be recognized but unilateral defects point to MD.

Zusammenfassung Die striatale Dopamin-D2-Rezeptoranreicherung von 123J-IBZM wurde bei 32 Patienten (18 ohne und 14 mit neuroleptischer Therapie) semiquantitativ unter Anwendung verschiedener ROI-Techniken ausgewertet. Ziel der Studie war es, die von verschiedenen Untersuchern gefundenen unterschiedlichen Quotienten (Striatum/Kortex) unter dem Aspekt der angewandten ROI-Technik zu untersuchen. Es konnte gezeigt werden, daß bei Verwendung des gleichen SPECT-Systems keine größeren Unterschiede zwischen Rechteck-ROI und manuell erstellten ROI gleicher Größe auftreten. Eine hochsignifikante Trennung zwischen behandelten und unbehandelten Patienten ergab sich für alle untersuchten Auswerteverfahren. Der ermittelte Quotient wird wesentlich durch das Auflösungsvermögen der Kamera und nur relativ geringfügig durch die verwendete ROI-Technik bestimmt. Die Quotienten verschiedener Arbeitsgruppen sind quantitativ nicht miteinander vergleichbar.

In den letzten Jahren erlauben Positronen-Emissions-Tomographie (PET) [5] und Single-Photon Emissions Tomographie (SPECT) [1] die in vivo-Darstellung der topographischen Verteilung zentraler Dopamin-Rezeptoren. Veränderungen der zentralen Dopamin-D2-Rezeptoren wurden bei verschiedenen Erkrankungen des ZNS nachgewiesen, so bei der Schizophrenie, Tardiven Dyskinesien, Morbus Parkinson, Chorea Huntington und anderen Erkrankungen der Basalganglien. Darüber hinaus spielt im Wirkprofil vieler Neuroleptika die Blockade postsynaptischer Dopamin-D2- Rezeptoren eine wichtige Rolle [4]. Bei 123J-IBZM (S-(-)-N-[(l-ethyl-2-pyrrolidinyl)methyl]-2-hydroxy-2-iodo-6-methoxybenzamid) handelt es sich um einen Radioliganden, der mit hoher Spezifität und hoher Affinität an zerebrale Dopamin-D2-Rezeptoren bindet und als Tracer für die SPECT verwendet werden kann [3]. Im Vergleich zur aufwendigen und kostenintensiven PET ermöglicht die SPECT eine Untersuchung größerer Patientenkollektive unter klinischen Routinebedingungen. Ein Nachteil der SPECT ist jedoch die fehlende Quantifizierung der Ergebnisse und schlechtere räumliche Auflösung. Ziel unserer Untersuchung war daher, ob mit der SPECT semiquantitative Daten der Dopamin-D2-Rezeptordichte unter klinischen Bedingungen erhoben werden können. Wir berichten unsere Ergebnisse bei den ersten 25 Patienten mit der Diagnose einer Schizophrenie nach DSM-III-R, bei denen eine 123J-IBZM-SPECT durchgeführt wurde.

Zusammenfassung Ziel der vorliegenden Untersuchung war es, zu prüfen, ob die HMPAO-SPECT zur Differenzierung zwischen der Demenz vom Alzheimer-Typ (DAT) und der Major Depression (MD) beitragen kann. Es wurden ECT-Befunde von 77 Patienten mit Gedächtnisstörungen beurteilt, davon hatten 48 eine DAT und 29 eine MD. Zunächst wurden die Defekte in der SPECT einer Hirn-Region zugeordnet und der Grad der Ausprägung (-1/-2/-3) bewertet. Anschließend wurden die einzelnen Befunde in eine von 7 Befundkategorien eingeordnet. In einigen dieser 7 Gruppen ergaben sich deutliche Häufungen der Fälle mit DAT bzw. MD. 35% aller DAT-Patienten wiesen bilaterale Defekte mit deutlicher (>-1) parietaler/parietotemporaler Minderperfusion auf, dagegen zeigte kein Patient mit MD dieses Muster. Unilaterale Defekte wiesen 62% der MD-, aber nur 31% der DAT-Patienten auf. Die Untersuchung zeigt, daß nur 35% der Patienten mit DAT das bislang als »pathognomonisch« bezeichnete Befundmuster aufwiesen. Dieses Perfusionsmuster kann aber - wenn es vorliegt - als sicheres Kriterium zur Abgrenzung gegen eine MD gewertet werden. Darüber hinaus lassen sich keine eindeutigen (»krankheitstypischen«) Perfusionsmuster erkennen, wenngleich unilaterale Defekte mehr auf eine MD hindeuten.

Mittels bildgebender Verfahren wie die Single-Photon-Ernission-Computed-Tomography (SPECT) und die Positron-Emission-Tomography (PET) konnten bei psychiatrischen Erkrankungen Perfusionsstörungen verschiedener Hirnareale nachgewiesen werden. Bei Schizophrenien hatte man in den früheren Studien Veränderungen im Frontallappen (Buchsbaum et al. 1982) gefunden. Diese Befunde konnten in den neueren Arbeiten nicht repliziert werden, hingegen scheint der Temporallappen besonders betroffen zu sein (Buchsbaum et al. 1990, deLisi et al. 1989) Bei affektiven Störungen sind Veränderungen im prefrontalen Cortex (Baxter et al. 1989, Cohen et al. 1989) und im Temporallappen (Post et al. 1987, Amsterdam et al. 1992) festgestellt worden. Bei den meisten der obengenannten Untersuchungen — besonders den PET-Studien — wurde meistens die Psychopathologie zum Zeitpunkt der Untersuchung vernachlässigt. Daher haben wir uns im Rahmen des jetzigen Projektes zum Ziel gesetzt, zu untersuchen, inwiefern eine spezifische bzw. globale Psychopathologie im Zusammenhang mit Durchblutungsverhältnissen (gemessen mit der HMPAO-SPECT-Technik) steht.