Marinus van Kroonenburgh

Delta-9-tetrahydrocannabinol-induced dopamine release as a function of psychosis risk: 18F-fallypride positron emission tomography study.

Cannabis use is associated with psychosis, particularly in those with expression of, or vulnerability for, psychotic illness. The biological underpinnings of these differential associations, however, remain largely unknown. We used Positron Emission Tomography and 18F-fallypride to test the hypothesis that genetic risk for psychosis is expressed by differential induction of dopamine release by Δ9-THC (delta-9-tetrahydrocannabinol, the main psychoactive ingredient of cannabis). In a single dynamic PET scanning session, striatal dopamine release after pulmonary administration of Δ9-THC was measured in 9 healthy cannabis users (average risk psychotic disorder), 8 patients with psychotic disorder (high risk psychotic disorder) and 7 un-related first-degree relatives (intermediate risk psychotic disorder). PET data were analyzed applying the linear extension of the simplified reference region model (LSRRM), which accounts for time-dependent changes in 18F-fallypride displacement. Voxel-based statistical maps, representing specific D2/3 binding changes, were computed to localize areas with increased ligand displacement after Δ9-THC administration, reflecting dopamine release. While Δ9-THC was not associated with dopamine release in the control group, significant ligand displacement induced by Δ9-THC in striatal subregions, indicative of dopamine release, was detected in both patients and relatives. This was most pronounced in caudate nucleus. This is the first study to demonstrate differential sensitivity to Δ9-THC in terms of increased endogenous dopamine release in individuals at risk for psychosis.

Correlation of intra-tumour heterogeneity on 18F-FDG PET with pathologic features in non-small cell lung cancer: A feasibility study

We evaluated the feasibility to correlate intra-tumour heterogeneity as visualized on 18F-FDG PET with histology for NSCLC. For this purpose we used an ex-vivo model. The procedure was feasible in all operated patients. We have shown that this method is suitable for correlating intra-tumour heterogeneity in tracer uptake with histology.

Increased cerebral serotonin-2A receptor binding in depressed patients with myocardial infarction

Serotonin (5-HT) has been implicated in the pathophysiology of depression. It is not known whether depression in post-myocardial infarction (MI) patients is also serotonin-mediated. In somatically healthy depressed persons, increased brain 5-HT(2A) receptor binding has been reported in some studies. In animal studies, decreased serotonin activity was found after induction of MI. In the present study, it was hypothesized that depressed post-MI patients would exhibit increased brain 5-HT(2A) receptor binding compared with non-depressed post-MI patients. Single photon emission computed tomography (SPECT) with the radioligand 123I-5-I-R91150, a 5-HT(2A) receptor antagonist, was used to study 5-HT(2A) receptor binding. SPECT scans were performed in nine depressed post-MI patients, 10 non-depressed post-MI patients and 10 healthy control subjects. Results were analysed using statistical parametric mapping. Depressed post-MI patients showed increased 5-HT(2A) receptor binding compared with non-depressed post-MI patients, and MI patients showed decreased 5-HT(2A) receptor binding compared with control persons. Both post-MI depression and MI seem to be associated with changes in 5-HT(2A) receptor binding.

FDG-PET-CT for staging of high-risk breast cancer patients reduces the number of further examinations: A pilot study

Abstract Aim. To determine the additional value of FDG-PET-CT as compared to conventional staging (CS) in high-risk breast cancer patients. Patients and methods. Thirty-one high-risk breast cancer patients, 14 of whom had recurrent breast cancer, were included in this study, which took place between June 2005 and March 2008. None of the patients had clinical signs of distant metastases. FDG-PET-CT scanning was added to CS, which consisted of a chest x-ray, liver ultrasonography or CT, and bone scintigraphy. Median follow-up was 17 months (6–41 months). FDG-PET-CT was considered to have additional value to CS if it led to a change in treatment plan or if it made additional examinations to confirm or deny findings on CS unnecessary. Results. FDG-PET-CT was considered to have additional value to CS in 13 patients (42% [95% CI: 23–61]). In five patients (16% [95% CI: 1–31]), FDG-PET-CT led to a change in treatment plan by identifying nodal metastases in the internal mammary chain (IMC; N = 3) or in the mediastinum (N = 2). In nine patients (29% [95% CI: 11–47]), FDG-PET-CT would have prevented the need for additional examinations; in seven of these nine patients, distant metastases were suggested in bone or liver on CS, but these did not show FDG uptake. Conclusions. FDG-PET-CT was found to have additional value to CS in 42% of the patients. To optimize cost-effectiveness, the main challenge now is to improve the selection of patients in whom FDG-PET-CT has additional value to CS.

A possible link between increased metabolic activity of fat tissue and aortic wall inflammation in subjects with COPD. A retrospective 18F-FDG-PET/CT pilot study

BACKGROUNDnFat tissue, and particularly visceral fat, is known to play a role in low grade systemic inflammation in COPD, and is likely to contribute to the excess cardiovascular comorbidity in COPD. Therefore, we aimed to study (18)FDG-PET-assessed inflammation of the aorta and the (visceral) fat, and evaluate its interrelations and differences in subjects with and without COPD.nnnMETHODSnWe retrospectively identified 42 patients (71% male, 48% current smokers, mean age 66.6 ± 8.3 years, mean BMI 25.1 ± 4.3 kg/m(2)), who underwent (18)F-FDG-PET/CT for suspected early stage bronchus carcinoma. COPD-diagnosis was based on spirometry and defined as FEV1/FVC < lower limit of normal. Inflammatory status of aortic and fat regions was defined as the average of obtained maximum target-to-background ratios (meanTBRmax). The TBR is the standardized uptake value (SUV) normalized to (18)F-FDG blood pool activity.nnnRESULTSnCompared to controls, patients with COPD (n = 19; 45%) had increased meanTBRmax of both the abdominal aorta (1.31 ± 0.14 vs. 1.49 ± 0.31; p = 0.02) and the abdominal visceral fat (0.28 ± 0.09 vs. 0.38 ± 0.18; p = 0.047), while inflammatory activity of the abdominal subcutaneous fat failed to show statistically significant differences (0.21 ± 0.09 vs. 0.24 ± 0.09; p = 0.345). In all patients, meanTBRmax of abdominal visceral fat was correlated with meanTBRmax of the abdominal aorta, independently of age and BMI (β = 0.590, p = 0.002).nnnCONCLUSIONnMetabolic activity of the abdominal aorta and visceral fat is increased in COPD patients compared to peers. The degree of visceral fat metabolic activity is associated with aortic inflammation. More prospective research is warranted concerning the role of visceral fat in the development of vascular comorbidity in COPD.

Aortic 18F-FDG uptake in patients suffering from granulomatosis with polyangiitis

PurposeThe objective of the study was to systematically assess aortic inflammation in patients with granulomatosis with polyangiitis (GPA) using 18F-2-deoxy-2-[18F]fluoro-D-glucose (FDG) positron emission tomography (PET)/CT.MethodsAortic inflammation was studied in PET/CT scans obtained from 21 patients with GPA; 14 patients with sarcoidosis were included as disease controls, 7 patients with stage I or II head and neck carcinoma ascertained during routine clinical practice were used as healthy controls (HC) and 5 patients with large vessel vasculitis (LVV) were used as positive controls. Aortic 18F-FDG uptake was expressed as the blood-normalized maximum standardized uptake value (SUVmax), known as the target to background ratio (mean TBRmax).ResultsThe mean TBRmax (interquartile range) of the aorta in patients with GPA, sarcoidosis, HC and LVV were 1.75 (1.32–2.05), 1.62 (1.54–1.74), 1.29 (1.22–1.52) and 2.03 (1.67–2.45), respectively. The mean TBRmax was significantly higher in patients suffering from GPA or LVV compared to HC (pu2009<u20090.05 and pu2009<u20090.005, respectively) and tended to be higher in patients suffering from sarcoidosis, but this did not reach statistical significance (pu2009=u20090.098). The mean TBRmax of the most diseased segment was significantly higher compared to HC [1.57 (1.39–1.81)] in LVV patients [2.55 (2.22–2.82), pu2009<u20090.005], GPA patients [2.17 (1.89–2.83), pu2009<u20090.005] and patients suffering from sarcoidosis [2.04 (1.88–2.20), pu2009<u20090.05]. In GPA patients, the mean TBRmax of the aorta was significantly higher in patients with previous renal involvement [2.01 (1.69–2.53)] compared to patients without renal involvement in the past [1.60 (1.51–1.80), pu2009<u20090.05]. Interrater reproducibility with a second reader was high (all intraclass correlation coefficients >0.9).ConclusionPatients suffering from GPA show marked aortic FDG uptake.

Retention of 99mTc-DMSA(III) and 99mTc-nanocolloid in different syringes affects imaging quality.

99mTc-dimercaptosuccinic acid [DMSA(III)] and colloidal human serum albumin (99mTc-nanocolloid) are widely used radiopharmaceuticals. Recently, in our institution we encountered image quality problems in DMSA scans after changing the brand of syringes we were using, which triggered us to look into the adsorption properties of syringes from different brands for 99mTc-DMSA(III) and 99mTc-nanocolloid. We also describe a clinical case in which adsorption of 99mTc-DMSA(III) caused inferior imaging quality. DMSA and nanocolloid were labeled with 99mTc following manufacturer guidelines. After synthesis, syringes with 99mTc-DMSA(III) and 99mTc-nanocolloid were stored for 15, 30, 60, and 120 min. We evaluated Luer Lock syringes manufactured by different brands such as Artsana, Henke-Sass-Wolf, B. Braun Medical N.V., CODAN Medizinische Geräte GmbH & Co KG, Becton Dickinson and Company, and Terumo Europe. Adsorption of 99mTc-DMSA(III) and 99mTc-nanocolloid was acceptably low for all syringes (<13%), except for two brands with 99mTc-DMSA(III) adsorption rates of 36 and 30%, respectively, and for one brand with a 99mTc-nanocolloid adsorption rate of 27%. Adsorption of 99mTc-DMSA(III) and 99mTc-nanocolloid reaches critical levels in syringes produced by two brands, potentially causing poor image quality – for example, in DMSA scans using pediatric radiopharmaceutical doses. It is advised to check the compatibility of any radiopharmaceutical with syringes as an integral part of the quality assurance program.