"Label and go"--a fast and easy radiolabelling method for pellets.

For the development and process optimization of pharmaceutical equipment, it is important to investigate the underlying processes. Taking the fluidized bed technology as an example, the study of particle flow pattern and convection of the particles within the functional unity is essential for construction and process improvement. With positron emission particle tracking (PEPT) it is possible to study the real-time particle motion with radiolabelled particles. We established a fast and simple labelling technique with [(18)F]fluoride for pellets composed of Avicel and anion exchange resin. The uptake of activity ranged from 1.3% to 1.7% per mg and 8.6% to 16.3% per pellet. A specific binding of [(18)F]fluoride with increasing degree of anion exchange resin in the pellets could be observed.

Simple and rapid preparation of [11C]DASB with high quality and reliability for routine applications.

[(11)C]DASB combines all major prerequisites for a successful SERT-ligand, providing excellent biological properties and in-vivo behaviour. Thus, we aimed to establish a fully automated procedure for the synthesis and purification of [(11)C]DASB with a high degree of reliability reducing the overall synthesis time while conserving high yields and purity. The optimized [(11)C]DASB synthesis was applied in more than 60 applications with a very low failure rate (3.2%). We obtained yields up to 8.9 GBq (average 5.3+/-1.6 GBq). Radiochemical yields based on [(11)C]CH(3)I, (corrected for decay) were 66.3+/-6.9% with a specific radioactivity (A(s)) of 86.8+/-24.3 GBq/micromol (both at the end of synthesis, EOS). Time consumption was kept to a minimum, resulting in 43 min from end of bombardment to release of the product after quality control. From our data, it is evident that the presented method can be implemented for routine preparations of [(11)C]DASB with high reliability.

Influence of escitalopram treatment on 5-HT 1A receptor binding in limbic regions in patients with anxiety disorders.

There is an increasing interest in the underlying mechanisms of the antidepressant and anxiolytic treatment effect associated with changes in serotonergic neurotransmission after treatment with selective serotonin (5-HT) reuptake inhibitors (SSRIs) in humans. The 5-HT(1A) receptor is known to play a crucial role in the pathophysiology of affective disorders, and altered 5-HT(1A) receptor binding has been found in anxiety patients. SSRI treatment raises the 5-HT level in the synaptic cleft and might change postsynaptic receptor densities. Therefore, our study in patients suffering from anxiety disorders investigated the effects of long-term treatment with escitalopram on the 5-HT(1A) receptor. A longitudinal positrone emission tomography (PET) study in 12 patients suffering from anxiety disorders was conducted. Two dynamic PET scans were performed applying the selective 5-HT(1A) receptor antagonist [carbonyl-(11)C]WAY-100635. Eight regions of interest were defined a priori (orbitofrontal cortex, amygdala, hippocampus, subgenual cortex, anterior and posterior cingulate cortex, dorsal raphe nucleus and cerebellum as reference). After the baseline PET scan, patients were administered escitalopram (average dose of 11.2+/-6.0 mg day(-1)) for a minimum of 12 weeks. A second PET scan was conducted after 109+/-27 days. 5-HT(1A) receptor binding potentials in 12 patients were assessed by PET applying the Simplified Reference Tissue Model.There was a significant reduction in the 5-HT(1A) receptor binding potential after a minimum of 12 weeks of escitalopram treatment in the hippocampus (P=0.006), subgenual cortex (P=0.017) and posterior cingulate cortex (P=0.034). The significance of the hippocampus region survived the Bonferroni-adjusted threshold for multiple comparisons. These PET data in humans in vivo demonstrate a reduction of the 5-HT(1A) binding potential after SSRI treatment.

Uptake of (18)F-FLT and (18)F-FDG in primary head and neck cancer correlates with survival.

UNLABELLED: The aim of the study was to determine the practicability of (18)F-FLT in tumours of the head and neck area in terms of visualization, a possible correlation between FLT uptake and proliferation fraction as determined by Ki-67 immunostaining, and if tumoural FLT-uptake has a prognostic meaning, as determined by a correlation to patient survival time. Results were compared to (18)F-FDG. PATIENTS, METHODS: 20 patients with previously untreated lesions of the head and neck area, which were clinically highly suspicious to be malignant, underwent PET scans with (18)F-FLT and (18)F-FDG, a CT of the head and neck area, and a biopsy. Tumour tracer uptake was determined by standardized uptake value (SUV) normalized to body weight and /non-tumor ratios (T/N). (18)F-FDG and (18)F-FLT uptake were compared with histopathologic and immunohistochemical results. RESULTS: 19 patients had malignant tumours; one patient had a benign cystadenoma (so called Warthin's tumour) of the parotid gland. One negative lesion turned out to be a malignant T1 stage squamous cell carcinoma in both PET scans, the Warthin's tumour was false positive with (18)F-FDG but showed only faint uptake with (18)F-FLT, resulting in a sensitivity of 95 % for both tracers. Of all lesions, maximum SUVs of (18)F-FLT ranged from 1.53 to 11.70 (mean +/- SD 5.81 +/- 2.28) those of FDG from 2.63 to 16.50 (mean +/- SD 8.91 +/- 3.58), p < 0.001. (18)F-FLT-T/N ranged from 0.94 to 5.85 (mean +/- SD, 3.18 +/- 1.21), (18)F-FDG-T/N was from 0.92 to 7.50 (mean +/- SD, 3.6 +/- 1.74), n.s. The mean survival time was 18 months in a maximum follow up time of 36 months. A significant correlation between both PET tracers and survival was detected, but no correlation between the amount of Ki-67 positive cells and FLT. CONCLUSION: In head and neck cancer in the primary setting (18)F-FLT does not provide additional visual information in comparison to (18)F-FDG.(18)F-FLT uptake is inversely correlated with patient survival, as well as (18)F-FDG.

Surgical target selection in cerebral glioma surgery: linking methionine (MET) PET image fusion and neuronavigation.

OBJECTIVE: The objective of this study was to investigate the histological correlate of (11)C-methionine (MET) PET uptake of brain gliomas by image fusion for navigated surgery. METHODS: Twenty-seven patients (18 male, 9 female; mean age 42 years; range 11-77 years; 8 low-grade and 11 high-grade astrocytomas or mixed gliomas, 8 oligodendrogliomas) underwent MET PET studies preoperatively. RESULTS: MET PET tumor uptake was detected in 26 of 27 patients (96.3%). The quantitative MET tumor standardized uptake value (SUV) ratio was significantly higher in malignant gliomas and oligodendrogliomas than in low-grade gliomas (2.76/2.62 vs. 1.67, p=0.03). Generally, qualitative visual grading of MET uptake revealed 2 main patterns: focal MET uptake in 12 and uniform global MET uptake in 11 patients. Focal uptake corresponded to malignant glioma histology in 66.7%, and uniform global uptake to oligodendroglial histology in 72.7%. In oligodendrogliomas, global MET uptake constituted 81.5% (range 53.8-135%) of the MRI T(1) tumor volume on average and was limited to the MRI FLAIR tumor volume in 86% (7/8) of patients. Tissue samples of focal MET uptake areas correlated with histological anaplasia in 66.6% (8/12 glioma patients), although 62.5% (5/8 patients) lacked MRI contrast enhancement. CONCLUSION: MET PET image fusion may facilitate the targeting of anaplastic foci in homogeneous MRI non-enhancing gliomas for biopsy, may identify oligodendroglial histology preoperatively as well as characterize biologically active tumor volumes within MRI T(1)/FLAIR tumor areas of candidate patients for resection.

[Diagnostic imaging in pregraduate integrated curricula]. / Radiologie in einem prägraduellen problembasiert-integrierten Medizincurriculum.

Pregraduate medical curricula are currently undergoing a reform process that is moving away from a traditional discipline-related structure and towards problem-based integrated forms of teaching. Imaging sciences, with their inherently technical advances, are specifically influenced by the effects of paradigm shifts in medical education. The teaching of diagnostic radiology should be based on the definition of three core competencies: in vivo visualization of normal and abnormal morphology and function, diagnostic reasoning, and interventional treatment. On the basis of these goals, adequate teaching methods and e-learning tools should be implemented by focusing on case-based teaching. Teaching materials used in the fields of normal anatomy, pathology, and clinical diagnosis may help diagnostic radiology to play a central role in modern pregraduate curricula.

13N-ammonia rest/stress PET: folic acid improves global coronary vasoreactivity in coronary artery disease patients with normal or elevated homocysteine levels.

AIM: Hyperhomocysteinaemia (Hhcy) is known to be an independent risk factor for vascular disease. Coronary flow reserve (CFR) measured by positron emission tomography (PET) is a sensitive method to monitor the effects of pharmacologic interventions in Hhcy. We assessed coronary vascular reactivity by PET in patients with coronary artery disease (CAD) dependent on their homocysteine (Hcy) levels before and under high dose folic acid supplementation therapy (FAST). PATIENTS, METHODS: Twelve patients with CAD underwent rest/adenosine (13) N-ammonia PET for quantification of myocardial blood flow (MBF) and CFR before and after nine weeks FAST (10 mg/day). RESULTS: Folate levels increased from 21 +/- 6 to 210 +/- 34 microg/l (+900%, p < 0.0001) while Hcy levels decreased from 12.1 +/- 3.6 to 9.1 +/- 3.1 micromol/l ( - 25%; p < 0.01). Global resting MBF remained nearly unchanged after FAST, while stress MBF (from 2.61 +/- 0.93 to 3.25 +/- 1.15 ml/g/min; p = 0.05) and CFR (from 3.00 +/- 0.76 to 3.72 +/- 0.93 ml/g/min; p < 0.05; +24%) significantly increased in patients with normal and elevated Hcy levels (cut off 12 micromol/l). An inverse relation was found between Hcy and CFR (R = - 0.53; p = 0.08) and between Hcy and MBF at rest (R = - 0.62; p < 0.05) at baseline conditions, not persisting after FAST. CONCLUSION: Coronary vascular reactivity can be improved by FAST in patients with CAD and normal or elevated Hcy levels. FAST might lower an increased cardiovascular risk in CAD patients possibly by mechanisms that are not related to Hcy.

FDG gamma camera PET equipped with one inch crystal and XCT. Assessment of myocardial viability.

UNLABELLED: Metabolic imaging with 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (FDG) is actually considered as the best method to detect and quantitatively assess myocardial tissue viability. The aim of this study was to investigate the accuracy of FDG gamma camera positron emission tomography (GCPET) imaging equipped with one inch NaI crystals in comparison to FDG dedicated PET (dPET) imaging as a "gold standard" in phantom and clinical studies. PATIENTS, METHODS: Nineteen patients with coronary artery disease (CAD) underwent both imaging modalities. Phantom and clinical GCPET imaging were performed with a dual-headed, coincidence based gamma camera equipped with 1 inch thick NaI crystals and an x-ray tube (XCT) for attenuation correction (AC), as well as with a dedicated PET scanner with AC. (99m)Tc tetrofosmin single-photon emission tomography (SPET) studies were performed for assessment of myocardial perfusion, with AC. RESULTS: Phantom studies showed a significant relation in segmental activity between FDG imaging with AC using GCPET and dPET (r = 0.91, p < 0.001). In clinical studies with AC correlation coefficients of mean segmental FDG uptake and regional defect size were r = 0.87 (p < 0.0001) and r = 0.83 (p < 0.0001), respectively. In regional analysis close agreement was even found in the most attenuated regions of the heart if AC was used in GCPET imaging. The overall agreement for detection of viable myocardium was 81% between FDG-dPET (AC) and FDG-GCPET (AC) and 74% between FDG-dPET (AC) and FDG-GCPET (NC). CONCLUSION: This study suggests that the assessment of myocardial metabolism by means of FDG is feasible with a coincidence based gamma camera equipped with 1 inch thick NaI crystals if AC is performed. The results reveal a close concordance and agreement between FDG-dPET (AC) and FDG-GCPET (AC) as compared to FDG-GCPET (NC).

Attenuation correction for myocardial perfusion imaging. A comparison between SPECT and PET imaging by polar map analysis.

AIM: We investigated the impact of photon attenuation in myocardial perfusion imaging with SPECT and PET in patients with coronary artery disease. In fact, the regional tracer distribution can be quantitatively assessed by polar map analysis if the effects of photon attenuation are accounted for. PET imaging permits accurate measurement of and correction for photon attenuation, whereas results of attenuation correction in SPECT imaging have been inconsistent. PATIENTS, METHODS: We compared photon attenuation in resting perfusion imaging studies with SPECT ((99m)Tc-sestamibi) and PET ((13)N-ammonia) from 21 patients. Transaxial images were reconstructed with and without attenuation correction and reoriented into short axis images. Polar map analysis was utilized to generate regional tracer uptake in six anatomical segments. RESULTS: Average segmental photon attenuation calculated as the ratio of counts in corrected and uncorrected images was 7.2 +/- 1.4 in SPECT and 14.0 +/- 3.1 in PET imaging (p < 0.01). This attenuation factor was significantly related to body mass index for both methods (p < 0.001). While attenuation correction for SPECT imaging did compensate for attenuation effects in the inferior wall (from -15% to +6% vs. PET), relative tracer uptake in the anterior wall in SPECT images was significantly reduced after attenuation correction (from -2% to -18% vs. PET, p < 0.01). CONCLUSION: Differential effects of attenuation correction for myocardial SPECT perfusion imaging need to be considered when algorithms designed to compensate effects of photon attenuation in SPECT imaging are employed in clinical practice.

18F-Fluoro-deoxy-glucose positron emission tomography in lymphoma of mucosa-associated lymphoid tissue: histology makes the difference.

BACKGROUND: The usefulness of 2-[fluorine-18]fluoro-2-deoxy-D-glucose Positron emission tomography (18F-FDG-PET) in lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is still a matter of debate, and conflicting results have been reported. We have evaluated whether the histological feature of plasmacytic differentiation (PD) might explain the heterogeneous behavior of MALT lymphoma regarding 18F-FDG uptake. PATIENTS AND METHODS: A total of 35 patients with a diagnosis of MALT lymphoma referred to our PET unit were studied. Whole-body 18F-FDG-PET scans were carried out on a General Electrics advanced PET scanner 40 min after i.v. injection of 300-380 MBq 18F-FDG. Images were reconstructed iteratively. In areas with focally elevated FDG uptake, standard uptake values (SUVs) were calculated. RESULTS: A total of 19 patients had MALT lymphoma with plasmacytic differentiation (pMALT), while MALT lymphoma without plasmacytic features was diagnosed in 16 patients. Sixteen of 19 patients with PD showed significant 18F-FDG uptake in involved sites (SUV: 3.5-11.7). By contrast, 13 of 16 patients with normal MALT lymphoma showed a false-negative 18F-FDG-PET result. Two of these patients disclosed no tracer uptake in the majority of involved sites apart from one single lesions, while three had a true-positive 18F-FDG-PET scan (SUV: 3.4-6.0). CONCLUSIONS: 18F-FDG-PET visualizes pMALT in a high proportion of patients, whereas FDG-PET results are significantly less reliable in typical MALT (P = 0.001). This finding may partly account for the heterogeneous results of 18F-FDG-PET-studies in MALT lymphoma.

Myocardial perfusion in patients with typical chest pain and normal angiogram.

BACKGROUND: Approximately 10-30% of patients with typical chest pain present normal epicardial coronaries. In a proportion of these patients, angina is attributed to microvascular dysfunction. Previous studies investigating whether angina is the result of abnormal resting or stress perfusion are controversial but limited by varying inclusion criteria. Therefore, we investigated whether microvascular dysfunction in these patients is associated with perfusion abnormalities at rest or at stress. PATIENTS AND METHODS: In 58 patients (39 female, 19 male, mean age 58+/-10 years) with angina and normal angiogram as well as 10 control patients with atypical chest pain and normal coronaries (six female, four male, mean age 53+/-11 years) myocardial blood flow (MBF) was measured at rest and under dipyridamole using 13N-ammonia PET. Resting MBF and coronary flow reserve (CFR) as the ratio of hyperaemic to resting MBF were corrected for rate-pressure-product (RPP): normalized resting MBF (MBFn)=MBFx10,000/RPP and CFRn=CFRxRPP/10,000. RESULTS: Sixteen/58 patients had a normal CFRn (=2.5; group I; CFRn: 3.1+/-0.88); the same as the controls (CFRn: 3.3+/-0.74). Forty-two/58 patients presented a reduced CFRn (group II; CFRn: 1.78+/-0.57). Group II had both a higher MBFn (group II: 1.30+/-0.33 vs. Group I: 1.03+/-0.26; P<0.05 and vs. controls: 1.07+/-0.19; P<0.01) and a lower hyperaemic MBF (group II: 2.25+/-0.76 mL g-1 min-1 vs. Group I: 3.07+/-0.78 mL g-1 min-1; P<0.001 and vs. controls: 3.41+/-0.94 mL g-1 min-1; P<0.0001). CONCLUSION: Impaired CFRn in patients with typical angina and normal angiogram is owing to both an increased resting and reduced hyperaemic MBF. Therefore, PET represents a prerequisite for further studies to optimize treatment in individuals with anginal pain and normal coronary angiogram.

18F-fluoro-deoxy-glucose positron emission tomography (18F-FDG-PET) visualizes follicular lymphoma irrespective of grading.

BACKGROUND: 18F-fluoro-deoxy-glucose positron emission tomography (18F-FDG-PET) has become a routine measure for staging and follow-up of patients with aggressive lymphoma. By contrast, its usefulness to visualize indolent lymphomas characterized by a lower cellular turnover has not clearly been defined. We have investigated accuracy and clinical usefulness of 18F-FDG-PET in patients with follicular lymphoma (FL). PATIENTS AND METHODS: A total of 64 patients with FL WHO grade I - III (48, 5, and 11 patients) were imaged at our institution to assess the value of 18F-FDG-PET for imaging of FL of different gradings. A total of 115 scans (48 before therapy and 67 for response assessment after treatment) were performed, and findings were compared to conventional staging including CT-scan of thorax and abdomen, sonography of lymph nodes and bone marrow biopsy. RESULTS: Overall, 18F-FDG-PET had a sensitivity of 98%, a specificity of 94%, a positive predictive value of 95% and a negative predictive value of 98%. These results were significantly more accurate (P = 0.023) than the conventional radiology studies. There was no significant difference (P = 0.093) in the accuracy between patients with indolent (WHO grade I and II) versus aggressive FL (WHO grade III). CONCLUSION: 18F-FDG-PET scan is a reliable method for staging and follow up of patients with nodal FL irrespective of tumor grading.

Gastrointestinal transit, release and plasma pharmacokinetics of a new oral budesonide formulation.

AIMS: The aims of the study were to: (1) evaluate the gastrointestinal transit, release and absorption of budesonide from tablets with a new multimatrix formulation (MMX) designed to release the drug throughout the whole colon, and (2) assess the influence of food on budesonide bioavailability. METHODS: Two phase I studies, each comprising 12 healthy males, were performed. Gastrointestinal transit of (153)Sm-labelled tablets containing 9 mg budesonide was evaluated by means of pharmaco-scintigraphy. The effect of food was tested by comparing plasma pharmacokinetics after intake of a high fat and high calorie breakfast with fasting controls. RESULTS: (153)Sm-labelled tablets reached the ascending colon after a mean +/- SD 9.8 +/- 6.9 h. Initial tablet disintegration was observed in the ileum in 42% and the ascending and transverse colon in 33% of subjects. Ninety-six per cent of the dose was absorbed into the systemic circulation during passage through the whole colon including the sigmoid. Food significantly decreased C(max) values from 1429 +/- 1014 to 1040 +/- 601 pg mL(-1) (P = 0.028) and AUC values from 14 814 +/- 11 254 to 13 486 +/- 9369 pg h(-1) mL(-1) (P = 0.008). Mean residence time and t(max) increased by 12-29%. There was no drug accumulation after 1 week of once daily oral administration of budesomide. CONCLUSIONS: MMX-budesonide tablets appear suitable for targeted colonic drug delivery. Transit parameters and low systemic bioavailability warrant further studies with the new formulation.

5-aminosalicylic acid release from a new controlled-release mesalazine formulation during gastrointestinal transit in healthy volunteers.

BACKGROUND: Mesalazine (5-aminosalicylic acid, 5-ASA) containing formulations represent a cornerstone in the treatment of inflammatory bowel diseases. A novel formulation with an Eudragit L/S mixture coating has been developed to provide selective release of 5-ASA to the ileo-caecal region and the colon. AIM: To determine the release of 5-ASA during the gastrointestinal transit. METHODS: A single oral dose of mesalazine EC 500 mg gastroresistant tablets (Asamax) was administered to eight healthy male volunteers. Gastrointestinal transit and tablet disintegration were monitored by scintigraphy. 5-ASA release was verified by assessing plasma pharmacokinetics. RESULTS: Initial tablet disintegration was observed 5.65 +/- 0.86 h after dosing, corresponding to the detection of 5-ASA in plasma. This occurred in the ileo-caecal region in three subjects and the ascending colon in the remaining five. The relative percentage of 5-ASA absorption was more pronounced in the ascending colon (41 +/- 27.4%) than the ileo-caecal region (6.6 +/- 9.2%). CONCLUSION: This mesalazine EC gastroresistant tablets release locally active 5-ASA specifically in the ileo-caecal region and the ascending colon.

Colonic spread and serum pharmacokinetics of budesonide foam in patients with mildly to moderately active ulcerative colitis.

BACKGROUND: Local treatment with foams in patients suffering from ulcerative proctitis or proctosigmoiditis is considered a rational treatment option. AIMS: To investigate colonic spread, safety, tolerability and acceptance of a newly developed budesonide foam formulation. METHODS: Twelve patients (four females, eight males) with acute proctosigmoiditis or left-sided ulcerative colitis were rectally administered a single dose of [99Tcm]-labelled budesonide foam (Budenofalk; Dr Falk Pharma GmbH, Freiburg, Germany) containing 2 mg budesonide in 20 mL foam after diagnostic colonoscopy. Thereafter, the colonic spread was assessed by means of gamma-scintigraphy for 6 h. Serum samples were taken simultaneously. RESULTS: Budesonide foam spread with a maximum between 11 and 40 cm, thus reaching the sigmoid colon in all patients. In some patients, the foam even extended into the distal third and the middle of the descending colon with maximum radioactivity at 4 h. Systemic budesonide absorption was rapid and pharmacokinetic data were comparable with published data on marketed budesonide enemas, with mean serum C(max) and AUC(0-8 h) values of 0.8 +/- 0.5 ng/mL and 3.7 +/- 1.9 ng h/mL, respectively. The new formulation was well accepted by all patients, who could retain the foam for at least 4 h. CONCLUSIONS: In the majority of patients, budesonide foam effectively spread up to the left-sided colon and thus qualifies for the local treatment of proctosigmoiditis.

Gastrointestinal transit and release of 5-aminosalicylic acid from 153Sm-labelled mesalazine pellets vs. tablets in male healthy volunteers.

BACKGROUND: Mesalazine (5-aminosalicylic acid)-containing formulations, designed to optimize drug delivery to the ileo-caecal region, represent a cornerstone in the treatment of inflammatory bowel diseases. AIM: : To test, by means of pharmaco-scintigraphy, whether novel mesalazine-containing pellets release 5-aminosalicylic acid in the same target region as mesalazine tablets (Salofalk). METHODS: Fourteen healthy male volunteers received a single dose of either pellets or tablets containing 500 mg of mesalazine and 2 mg of 152Sm2O3 with a 1-week washout period. The gastrointestinal transit of 153Sm, incorporated into the formulations, was followed by gamma-scintigraphy. Mesalazine release was verified by assessing 5-aminosalicylic acid plasma pharmacokinetics. RESULTS: The formulations reached the ileo-caecal target region almost at the same time (3.3 +/- 1 and 3.8 +/- 1 h for pellets and tablets, respectively). Plasma 5-aminosalicylic acid tmax values were comparable and corresponded to the time during which the formulations were located in the target region. Plasma AUC values were significantly lower for pellets, which might be explained by a more prolonged release of 5-aminosalicylic acid. CONCLUSIONS: Novel mesalazine pellets and Salofalk tablets release active 5-aminosalicylic acid in the same target region and pass through the gastrointestinal tract under fasting conditions in healthy volunteers in a comparable time. From a comparison of in vitro dissolution and plasma concentration data, a slower and more prolonged release of 5-aminosalicylic acid from pellets is suggested.

Prognostic value of FDG-PET in malignant lymphoma.

Lymphomas have represented an indication for nuclear medicine investigations for 30 years. Gallium-67 scintigraphy has been shown to be a valuable complementary method in Hodgkin's disease and non-Hodgkin lymphoma for detecting viable residual lesions after chemotherapy and for diagnosis of a relapse. Thallium-201 is of interest in differentiating cerebral lymphomas from infectious lesions in AIDS patients but less useful in extra-cerebral lymphomas. PET with fluorine-18-FDG is more accurate than 67Ga in lymphoma. In patients with a positive PET scan after chemotherapy an early relapse occurs in up to 100%, while more than 80% of patients with a negative PET will have a long-term remission. Most studies show that FDG-PET is significantly correlated with patient outcome whereas there is much weaker or even no correlation for CT. The main reason is that PET is not bound to morphological criteria like lymph node size while CT is often not able to differentiate between residual tumour and post-therapeutic fibrosis. Therefore, based on a considerable number of clinical studies, FDG-PET gains increasing significance for staging, restaging and therapy monitoring in malignant lymphomas.

Gastrointestinal transit and 5-ASA release from a new mesalazine extended-release formulation.

BACKGROUND: Mesalazine (5-aminosalicylic acid, 5-ASA)-containing formulations represent a cornerstone in the treatment of inflammatory bowel diseases. Recently, a new formulation has been developed to provide selective and more homogeneous release of 5-ASA compared to traditional systems. METHODS: In a first study, gastrointestinal transit was followed by gamma-scintigraphy after single-dose application of tablets containing 1200 mg mesalazine to 12 healthy male volunteers. 5-ASA release was verified by the assessment of plasma pharmacokinetics. In a second, 7-day, multiple-dose study, the steady state plasma pharmacokinetics, urinary excretion and safety profile were characterized after twice-daily tablet administration to 12 healthy volunteers. RESULTS: Tablet erosion started after 6.9 +/- 1.1 h in the ascending or transverse colon. Radioactivity spread homogeneously throughout the colon, indicating the sustained release of active 5-ASA. Plasma kinetics indicated an earlier initial absorption of 5-ASA, i.e. during transit of the small intestine and ileum. Mean Cmax values (350.6 +/- 322.6 ng/mL) were observed during location in the ileo-caecal region. The mean relative absorption of 5-ASA was 19.9 +/- 18.2% in the small intestine and ileum and 80.1 +/- 18.2% in the colon. CONCLUSIONS: The administration of the new mesalazine formulation was well tolerated, and 5-ASA was continuously released along the whole colon, a favourable prerequisite for the therapy of distally located inflammatory bowel disease.

18F-fluoro-deoxy-glucose positron emission tomography (18F-FDG-PET) for assessment of enteropathy-type T cell lymphoma.

BACKGROUND AND AIMS: Enteropathy-type T cell lymphoma (ETCL) represents a relatively rare disease, accounting for less than 1% of non-Hodgkin's lymphomas. ETCL is an aggressive lymphoma which may either present de novo or arise in the context of longstanding or untreated coeliac disease (CD). The aim of this study was to evaluate the potential of 18F-fluoro-deoxy-glucose positron emission tomography (18F-FDG-PET) for imaging of ETCL. Furthermore, we wished to evaluate whether the presence of CD might provide a potential diagnostic obstacle to imaging of lymphoma due to unspecific 18F-FDG uptake and whether accumulation of 18F-FDG within the gut correlates with activity of CD. PATIENTS AND METHODS: We retrospectively analysed patients with ETCL and individuals suffering from CD undergoing 18F-FDG-imaging at our PET unit. Material for histological reassessment by a reference pathologist had to be available for inclusion of patients in the analysis. Whole body 18F-FDG-PET scans were performed 40 minutes following injection of 300-380 MBq of 18F-FDG. Images were reconstructed iteratively. In areas with focally elevated FDG uptake and in case of diffusely elevated intestinal 18F-FDG accumulation, standard uptake values (SUVs) were calculated. RESULTS: During a period of two years, five patients (one male, four female) with a mean age of 56.4 years (range 44-62) with a diagnosis of ETCL underwent 18F-FDG-PET. Four of these patients were imaged before application of cytotoxic treatment while one patient had regular PET scans for follow up. All four patients undergoing pre-therapeutic imaging showed markedly elevated intestinal 18F-FDG uptake, with a maximal SUV of 6.4-8.0 (mean 7.15 (SD 0.82)). The patient imaged following surgery and cytotoxic therapy had no pathologic 18F-FDG uptake which was found to correlate with normal duodenal mucosa, as evidenced by repeated biopsies and conventional imaging methods. During the same time span, 12 patients (five male, seven female) with a mean age of 63.8 years (range 42-82) suffering from CD were imaged. Four of these patients showed no elevated intestinal 18F-FDG uptake while five had minor diffuse intestinal 18F-FDG accumulation with SUVs ranging between 2.2 and 4.6 (mean 3.4 (SD 0.89)). In the remaining three patients with diffuse intestinal 18F-FDG uptake, no SUV could be calculated. SUVs in patients with ETCL were remarkably higher than in patients suffering from CD (p=0.011), irrespective of the activity of CD at the time of imaging. CONCLUSION: In spite of the relatively small number of patients, our results clearly indicate the potential value of 18F-FDG-PET for diagnosing and imaging ETCL. In addition, the data also suggest that 18F-FDG-PET may lead to early diagnosis in individuals developing ETCL in the context of longstanding CD. This is due to the fact that 18F-FDG does not appear to significantly accumulate in the gut of patients with CD, irrespective of disease activity.