Influence of PET reconstruction parameters on the TrueX algorithm. A combined phantom and patient study.

UNLABELLED: With the increasing use of functional imaging in modern radiotherapy (RT) and the envisaged automated integration of PET into target definition, the need for reliable quantification of PET is growing. Reconstruction algorithms in new PET scanners employ point-spread-function (PSF) based resolution recovery, however, their impact on PET quantification still requires thorough investigation. PATIENTS, MATERIAL, METHODS: Measurements were performed on a Siemens PET/CT using an IEC phantom filled with varying activity. Data were reconstructed using the OSEM (Gauss filter) and the PSF TrueX (Gauss and Allpass filter) algorithm with all available products of iterations (i) and subsets (ss). The recovery coeffcient (RC) and threshold defining the real sphere volume were determined for all settings and compared to the clinical standard (4i21ss). PET acquisitions of eight lung patients were reconstructed using all algorithms with 4i21ss. Volume size and tracer uptake were determined with different segmentation methods. RESULTS: The threshold for the TrueX was lower (up to 40%) than for the OSEM. The RC for the different algorithms and filters varied. TrueX was more sensitive to permutations of i and ss and only the RC of the OSEM stabilised with increasing number. For patient scans the difference of the volume and activity between TrueX and OSEM could be reduced by applying an adapted threshold and activity correction. CONCLUSION: The TrueX algorithm results in excellent diagnostic image quality, however, guidelines for native algorithms have to be extended for PSF based reconstruction methods. For appropriate tumour delineation, for the TrueX a lower threshold than the 42% recommended for the OSEM is necessary. These filter dependent thresholds have to be verified for different scanners prior to using them in multicenter trials.

Imaging of highly malignant osteosarcoma with iodine-123-vascular endothelial growth factor.

OBJECTIVE: Vascular endothelial growth factor (VEGF) is an important angiogenic factor, and its receptors have been shown to be overexpressed in various human carcinomas. In this study, we investigated the role of scanning with iodine-123 ((123)I)-labelled VEGF(165) in patients with highly malignant osteosarcoma. METHODS: Two patients (a 15-year-old female and a 14-year-old male) with osteosarcoma were injected with 140 MBq [<130 pmol (<5 µg) VEGF(165) per patient] of (123)I-VEGF(165). Dynamic acquisition was initiated immediately after administration and carried out until 30 min after injection. Whole-body images were done in anterior and posterior views at various time points. All patients underwent single-photon emission tomography imaging. RESULTS: (123)I-VEGF(165) scans were positive in these patients. Sequential images clearly showed increased (123)I-VEGF(165) activity in osteosarcoma lesions. The tumour lesions were still visualized in whole-body images and single-photon emission tomography examinations 2 h after injection. Intravenous injection of (123)I-VEGF(165) did not cause any side effects. CONCLUSION: Our results suggest that (123)I-VEGF(165) receptor scintigraphy may be useful for the visualization of highly malignant osteosarcoma and/or metastasis and the angiogenic activity of the tumour.

Improved quality of life in patients treated with Peptide radionuclides.

Peptide receptor radionuclide therapy (PRRT) has recently been established as an important treatment modality for somatostatin receptor (SSTR)-positive tumors. The purpose of this study was to evaluate the clinical response, side-effects as well as the quality of life following (90)Y-DOTA-lanreotide (DOTALAN) and/or (90)Y-DOTA-Tyr (3)-DPhe(1)-octreotide (DOTATOC) therapy in patients with progressive metastatic disease during a 6-year follow-up period. Following dosimetric evaluation with (111)In-DOTALAN and (111)In-DOTATOC, 13 patients with estimated absorbed tumor doses of >5 Gy/GBq (carcinoid, n = 5; radioiodine-negative thyroid cancer, n = 4; gastrinoma, n = 1; insulinoma, n = 1; glucagonoma, n = 1; glomus jugularis tumor, n = 1) were assigned for PRRT. A dose of 925 MBq of (90)Y-DOTALAN (four patients) or 1.85-3.7 GBq of (90)Y-DOTATOC (10 patients) was administered intravenously and repeated every 4-8 weeks. Tumor dosimetry was performed prior to and under therapy, re-staging every 2-3 months. Pain intensity, Karnofsky score and general symptoms were evaluated in order to determine quality of life. Patients were followed until death. Altogether, 53 infusions of PRRT (1.85-14.1 GBq) were administered. After the first follow-up of 3 months of (90)Y-DOTALAN therapy, stable disease (SD) was observed in one patient and progressive disease (PD) in three patients. With (90)Y-DOTATOC therapy, SD was found in all 10 patients. During the re-evaluation period (4-27 months), one patient had to be shifted from (90)Y-DOTALAN to (90)Y-DOTATOC therapy due to reduced (111)In-DOTALAN uptake after 5.5 GBq. In the first 6 months after PRRT with DOTATOC, SD was found in nine of 10 patients and PD in one patient. Thereafter, SD was observed in two patients and PD in eight patients. Nine of 13 patients after PRRT with either DOTALAN or DOTATOC died. None of the patients had experienced severe acute hematological side-effects. Transient thrombocytopenia or lymphocytopenia was seen in 10 patients after 3.7 GBq, and a skin reaction in one patient. Total accumulated kidney dose ranged between 4 and 64 Gy, with reduced creatinine clearance in two patients. Pain relief was achieved in three of three patients after ~3.7 GBq ERT within 4-6 months. Appetite, weight, Karnofsky score and general well-being had improved in patients with SD during and after therapy. Based on the results of this study conducted on a small group of patients, we conclude that PRRT may offer an alternative treatment option for SSTR-positive tumors, with only mild transient side-effects and a marked improvement in the quality of life.

Optimization of the radiosynthesis of the Alzheimer tracer 2-(4-N-[11C]methylaminophenyl)-6-hydroxybenzothiazole ([11C]PIB).

[(11)C]PIB is still the standard PET compound for Alzheimer imaging targeting beta-amyloid plaques. We aimed to establish a fully-automated procedure for the synthesis and purification of [(11)C]PIB with a high degree of reliability and improved specific activity as well as a suitable and fast quality control assay. The optimum reaction conditions were 75°C, 4 mg/mL precursor yielding at 48.0±2.7% (EOS, based on [(11)C]CH(3)OTf, corrected for decay), 183±14 GBq/µmol specific activity and >99% radiochemical purity. Time consumption was kept to a minimum (40 min from EOB) and overall yields were enough to serve 2 consecutive patients with a single preparation.

Assessment of left ventricular volumes, ejection fraction and mass. Comparison of model-based analysis of ECG-gated (99m)Tc-SPECT and ¹8F-FDG-PET.

AIM: We compared and delineated possible differences of model-based analysis of ECG-gated SPECT using (99m)Tc-sestamibi (Tc-SPECT) with ECG-gated ¹8F-fluorodeoxyglucose-PET (FDG-PET) for determination of end-diastolic (EDV) and end-systolic (ESV) cardiac volumes, left ventricular ejection fraction (LVEF), and myocardial mass (LVMM). PATIENTS, METHODS: 24 patients (21 men; age: 54±12years) with coronary artery disease underwent Tc-SPECT and FDG-PET imaging for evaluation of myocardial perfusion and viability. By using model-based analysis EDV, ESV, LVEF and LVMM were calculated from short axis images of both Tc-SPECT and FDG-PET. RESULTS: Left ventricular volumes by Tc-SPECT and FDG-PET were 176±60 ml and 181±59 ml for EDV, and 97±44 ml and 103±45 ml for ESV respectively, LVEF was 47±8% by Tc-SPECT and 45±9% by FDG-PET. The LVMM was 214±40 g (Tc-SPECT) and 202±43 g (FDG-PET) (all p = NS, paired t-test). A significant correlation was observed between Tc-SPECT and FDG-PET imaging for calculation of EDV (r = 0.93), ESV (r = 0.93), LVEF (r = 0.83) and LVMM (r = 0.72). CONCLUSION: ECG-gated Tc-SPECT and FDG-PET using two tracers with different characteristics (perfusion versus metabolism) showed close agreement concerning measurements of left ventricular volumes, contractile function and myocardial mass by using a model-based analysis.

"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.

Amyloid PET and MRI in Alzheimer's disease and mild cognitive impairment.

The neurodegenerative disorder Alzheimer's disease (AD) is the most common form of dementia. It is characterized by progressive impairment of cognitive functions and behavior. To distinguish clinically AD from other forms of dementia is an ongoing challenge. In addition, although mild cognitive impairment (MCI) is recognized as a risk factor for dementia, it remains a challenge to predict on an individual level who will convert to become demented. Amyloid beta (Abeta) is one of the crucial pathological findings in AD. Recently, amyloid tracers for PET imaging have been developed successfully which may offer the unique possibility for measuring fibrillar Abeta load in the living brain. Therefore, in the near future positron emission tomography (PET) may become an important tool for in vivo amyloid imaging contributing to early (differential) diagnosis as well as evaluation of treatment response in AD. Moreover, Abeta may play a role in prediction the conversion of MCI to AD. In this paper we review the recent development of the molecular imaging technique PET and its different radiopharmaceuticals on the trail for imaging amyloid in AD and the conversion of MCI to AD.

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.

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.

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.

In vivo imaging of serotonin transporter occupancy by means of SPECT and [123I]ADAM in healthy subjects administered different doses of escitalopram or citalopram.

BACKGROUND: Escitalopram is a dual serotonin reuptake inhibitor (SSRI) approved for the treatment of depression and anxiety disorders. It is the S-enantiomer of citalopram, and is responsible for the serotonin reuptake activity, and thus for its pharmacological effects. Previous studies pointed out that clinically efficacious doses of other SSRIs produce an occupancy of the serotonin reuptake transporter (SERT) of about 80% or more. The novel radioligand [123I]ADAM and single photon emission computer tomography (SPECT) were used to measure midbrain SERT occupancies for different doses of escitalopram and citalopram. METHODS: Twenty-five healthy subjects received a single dose of escitalopram [5 mg (n=5), 10 mg (n=5), and 20 mg (n=5)] or citalopram [(10 mg (n=5) and 20 mg (n=5)]. Midbrain SERT binding was measured with [(123)I]ADAM and SPECT on two study days, once without study drug and once 6 h after single dose administration of the study drug. The ratio of midbrain-cerebellum/cerebellum was the outcome measure (V3") for specific binding to SERT in midbrain. Subsequently, SERT occupancy levels were calculated using the untreated baseline level for each subject. An Emax model was used to describe the relationship between S-citalopram concentrations and SERT occupancy values. Additionally, four subjects received placebo to determine test-retest variability. RESULTS: Single doses of 5, 10, or 20 mg escitalopram led to a mean SERT occupancy of 60+/-6, 64+/-6, and 75+/-5%, respectively. SERT occupancies for subjects treated with single doses of 10 and 20 mg citalopram were 65+/-10 and 70+/-6%, respectively. A statistically significant difference was found between SERT occupancies after application of 10 and 20 mg escitalopram, but not for 10 and 20 mg citalopram. There was no statistically significant difference between the SERT occupancies of either 10 mg citalopram or 10 mg escitalopram, or between 20 mg citalopram and 20 mg escitalopram. Emax was slightly higher after administration of citalopram (84%) than escitalopram (79%). In the test-retest study, a mean SERT "occupancy" of 4% was found after administration of placebo, the intraclass correlation coefficient was 0.92, and the repeatability coefficient was 0.25. CONCLUSION: SPECT and [123I]ADAM were used to investigate SERT occupancies after single doses of escitalopram or citalopram. The test-retest study revealed good reproducibility of SERT quantification. Similar SERT occupancies were found after administration of equal doses (in respect to mg) of escitalopram and citalopram, giving indirect evidence for a fractional blockade of SERT by the inactive R-citalopram.

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.

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.

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.

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.

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.

Iodine-123-vascular endothelial growth factor-165 (123I-VEGF165). Biodistribution, safety and radiation dosimetry in patients with pancreatic carcinoma.

AIM: Imaging with radiolabelled vascular endothelial growth factor (VEGF) has been developed for the localisation and diagnosis of a variety of human solid tumors including gastrointestinal tumors. METHODS: In this study we investigated the biodistribution, safety and absorbed dose of iodine-123 radiolabelled VEGF(165) ((123)I-VEGF(165)) in 9 patients with pancreatic carcinoma. Following intravenous administration of (123)I-VEGF(165) (189+/-17 MBq; <130 pmole (<5 microg) VEGF(165) per patient), sequential images were recorded during the initial 30 min PI. Serial whole-body images were acquired in anterior and posterior views at various time points. All patients underwent single-photon emission tomography (SPET) imaging. Dosimetry calculations were performed on the basis of gamma camera data. Estimates of radiation absorbed dose were calculated using the MIRDOSE 3 program. RESULTS: The highest absorbed organ doses were found to be thyroid (0.058+/-0.004 mGy/MBq), spleen (0.046+/- 0.017 mGy/MBq), urinary bladder (0.04+/-0.02 mGy/MBq), lungs (0.034+/-0.009 mGy/MBq) and kidneys (0.033+/-0.005 mGy/MBq). The effective dose was estimated to be 0.017+/-0.002 mSv/MBq. A majority of primary pancreatic tumors and their metastases were visualized by (123)I-VEGF(165) scan. CONCLUSION: In vitro binding results confirmed specific binding of (123)I-VEGF(165) to pancreatic tumor cells and tissues. (123)I-VEGF(165) shows favorable dosimetry and is a safe radiopharmaceutical that may be of potential value for the imaging of VEGF receptor status in vivo.

Value of combined XCT/SPECT technology for avoiding false positive planar (123)I-MIBG scintigraphy.

AIM: The clinical value of combined XCT/SPECT technology in a single device in patients undergoing (123)I-MIBG scintigraphy was analyzed. METHODS: 31 patients (19 men, 12 women; mean age 55 years, range: 31-79 years) demonstrating focal accumulation in planar (123)I-MIBG scan were further investigated with a double headed gamma camera with an X-ray tomograph mounted on the same gantry (GE Medical Systems, Millennium VG with Hawkeye, Milwaukee, USA) for anatomical definition of the focal (123)I-MIBG uptake. The patients were referred to (123)I-MIBG scintigraphy because of biochemically (81%) and/or clinically (19%) suspected pheochromocytoma. RESULTS: In 23 out of 31 patients (74%) the fused images demonstrated physiological accumulation (i. e. intestinal, renal) of (123)I-MIBG. In two patients (6%) suspected adrenal MIBG-accumulation was caused by inhomogeneous liver uptake. In two patients (6%) focal abdominal accumulation was correctly localised in the adrenal glands. Furthermore, the differentiation of bone metastasis from a local recurrence for phaeochromocytoma was accurately possible for two patients (6%). Adrenal lesions mimicking liver foci were correctly localised in the remaining two patients (6%). CONCLUSION: Our study demonstrates the clinical value of XCT/SPECT in a single device in patients demonstrating focal (123)I-MIBG uptake in planar scintigraphy. The combined XCT/SPECT technology provides a higher diagnostic accuracy.

Combined transmission and (99m)Tc-sestamibi emission tomography for localization of mediastinal parathyroid glands.

AIM: Although parathyroid scintigraphy using (99m) Tc-sestamibi is considered the best preoperative localization method for hyperfunctioning parathyroid tissue it lacks the anatomical details required for successful, minimal invasive surgery of ectopic parathyroid lesions. This study presents the role of combined SPECT/X-ray-CT imaging in a single device for localization of mediastinal parathyroid glands. METHODS: (99m) Tc-sestamibi SPECT/X-ray-CT was performed by gamma camera-mounted anatomical X-ray tomography (GMAXT; GE Medical systems, Millenium VG with Hawkeye) in four patients with ectopic parathyroid glands (two patients with primary, two with persistent secondary hyperparathyroidism). The device contains an X-ray tube and a set of detectors that rotate around the patient combined with a gamma camera. For comparison with GMAXT addition-ally high resolution computed tomography images of the neck and mediastinum were performed. RESULTS: Correct preoperative localization was achieved. The parathyroid glands were located in the anterior mediastinum. High resolution computed tomography could not provide further details. Three patients were operated by a minimal invasive open and one patient by a transsternal approach because of concomitant aortic valve replacement. CONCLUSION: (99m)Tc-sestamibi/X-ray-CT fusion imaging in a single device can accurately localise ectopic or supernumerary mediastinal parathyroid tumours in primary and secondary hyperparathyroidism. Morbidity,radiation exposure, time, and costs are reduced by avoiding multiple diagnostic examinations and minimal invasive parathyroid surgery becomes possible.