Evaluating repetitive 18F-fluoroazomycin-arabinoside (18FAZA) PET in the setting of MRI guided adaptive radiotherapy in cervical cancer.

BACKGROUND: The aim of this pilot study was to assess tumour hypoxia in patients with cervical cancer before, during and after combined radio-chemotherapy and Magnetic Resonance Imaging (MRI) guided brachytherapy (BT) by use of the hypoxia Positron Emission Tomography (PET) tracer (18)F-fluoroazomycin-arabinoside ((18)FAZA ). MATERIAL AND METHODS: Fifteen consecutive patients with locally advanced cervical cancer referred for definitive radiotherapy (RT) were included in an approved clinical protocol. Stage distribution was 3 IB1, 1 IB2, 10 IIB, 1 IIIB, tumour volume was 55 cm(3) (+/- 67, SD). Dynamic and static (18)FAZA -PET scans were performed before, during and after external beam therapy (EBRT) and image guided BT +/- concomitant cisplatin. Dose was prescribed to the individual High Risk Clinical Target Volume (HR CTV) taking into account the dose volume constraints for adjacent organs at risk. RESULTS: Five patients had visually identifiable tumours on (18)FAZA -PET scans performed prior to radio-chemotherapy and four patients before brachytherapy. One of five (18)FAZA PET positive patients had incomplete remission three months after RT, one had regional recurrence. Four of ten (18)FAZA-PET negative patients developed distant metastases. The one patient with incomplete remission received 69 Gy (D90) in the HR CTV, whereas all other patients received mean 99 Gy (+/-12, SD). CONCLUSION: PET imaging with (18)FAZA is feasible in patients with cancer of the uterine cervix. However, its predictive and prognostic value remains to be clarified. This applies in particular for the additional value of (18)FAZA-PET compared to morphologic repetitive MRI within the setting of image guided high dose radiotherapy which may contribute to overcome hypoxia related radioresistance.

The serotonin-1A receptor distribution in healthy men and women measured by PET and [carbonyl-11C]WAY-100635.

PURPOSE: The higher prevalence rates of depression and anxiety disorders in women compared to men have been associated with sexual dimorphisms in the serotonergic system. The present positron emission tomography (PET) study investigated the influence of sex on the major inhibitory serotonergic receptor subtype, the serotonin-1A (5-HT(1A)) receptor. METHODS: Sixteen healthy women and 16 healthy men were measured using PET and the highly specific radioligand [carbonyl-(11)C]WAY-100635. Effects of age or gonadal hormones were excluded by restricting the inclusion criteria to young adults and by controlling for menstrual cycle phase. The 5-HT(1A) receptor BP(ND) was quantified using (1) the 'gold standard' manual delineation approach with ten regions of interest (ROIs) and (2) a newly developed delineation method using a PET template normalized to the Montreal Neurologic Institute space with 45 ROIs based on automated anatomical labeling. RESULTS: The 5-HT(1A) receptor BP(ND) was found equally distributed in men and women applying both the manual delineation method and the automated delineation approach. Women had lower mean BP(ND) values in every region investigated, with a borderline significant sex difference in the hypothalamus (p = 0.012, uncorrected). There was a high intersubject variability of the 5-HT(1A) receptor BP(ND) within both sexes compared to the small mean differences between men and women. CONCLUSIONS: To conclude, when measured in the follicular phase, women do not differ from men in the 5-HT(1A) receptor binding. To explain the higher prevalence of affective disorders in women, further studies are needed to evaluate the relationship between hormonal status and the 5-HT(1A) receptor expression.

Preparation and first evaluation of [(18)F]FE@SUPPY: a new PET tracer for the adenosine A(3) receptor.

INTRODUCTION: Changes of the adenosine A(3) receptor subtype (A3AR) expression have been shown in a variety of pathologies, especially neurological and affective disorders, cardiac diseases and oncological and inflammation processes. Recently, 5-(2-fluoroethyl) 2,4-diethyl-3-(ethylsulfanylcarbonyl)-6-phenylpyridine-5-carboxylate (FE@SUPPY) was presented as a high-affinity ligand for the A3AR with good selectivity. Our aims were the development of a suitable labeling precursor, the establishment of a reliable radiosynthesis for the fluorine-18-labeled analogue [(18)F]FE@SUPPY and a first evaluation of [(18)F]FE@SUPPY in rats. METHODS: [(18)F]FE@SUPPY was prepared in a feasible and reliable manner by radiofluorination of the corresponding tosylated precursor. Biodistribution was carried out in rats, and organs were removed and counted. Autoradiography was performed on rat brain slices in the presence or absence of 2-Cl-IB-MECA. RESULTS: Overall yields and radiochemical purity were sufficient for further preclinical and clinical applications. The uptake pattern of [(18)F]FE@SUPPY found in rats mainly followed the described mRNA distribution pattern of the A3AR. Specific uptake in brain was demonstrated by blocking with a selective A3AR agonist. CONCLUSION: We conclude that [(18)F]FE@SUPPY has the potential to serve as the first positron emission tomography tracer for the A3AR.

Metabolism and autoradiographic evaluation of [(18)F]FE@CIT: a Comparison with [(123)I]beta-CIT and [(123)I]FP-CIT.

PURPOSE: Since the late 1980s, cocaine analogues based on the phenyltropane structure, such as [(11)C]CFT and [(123)I]beta-CIT have been used for the imaging of the dopamine transporter. FE@CIT (fluoropropyl ester) and FP-CIT (N-fluoropropyl derivative) are further analogues. The aim of this study was to (1) evaluate and compare the metabolic stability of beta-CIT, FP-CIT and FE@CIT against carboxyl esterases and (2) evaluate selectivity of [(18)F]FE@CIT compared to [(123)I]beta-CIT and [(123)I]FP-CIT using autoradiography. METHODS: In vitro enzymatic hydrolysis assays were performed using different concentrations of beta-CIT, FE@CIT and FP-CIT with constant concentrations of carboxyl esterase. Autoradiography was performed on coronal 20-microm rat brain sections incubated with different radioactivity concentrations of [(123)I]beta-CIT, [(123)I]FP-CIT or [(18)F]FE@CIT and, additionally, with 3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile [serotonin transporter (SERT)] and nisoxetine [norepinephrine transporter (NET)] for blocking experiments. RESULTS: In vitro assays showed Michaelis-Menten constants of 175 micromol (beta-CIT), 183 micromol (FE@CIT) and 521 micromol (FP-CIT). Limiting velocities were 0.1005 micromol/min (beta-CIT), 0.1418 micromol/min (FE@CIT) and 0.1308 micromol/min (FP-CIT). This indicates a significantly increased stability of FP-CIT, whereas carboxyl esterase stability of beta-CIT and FE@CIT showed no significant difference. Autoradiographic analyses revealed a good correlation between dopamine transporter (DAT)-rich regions and the uptake pattern of FE@CIT. Blocking experiments showed a higher DAT selectivity for [(18)F]FE@CIT than for the other two tracers. CONCLUSION: We found that (1) the metabolic stability of FE@CIT was comparable to that of beta-CIT, whereas FP-CIT showed higher resistance to enzymatic hydrolysis; and (2) the overall uptake pattern of [(18)F]FE@CIT on brain slices was comparable to that of [(123)I]beta-CIT and [(123)I]FPCIT. After blocking of NET and SERT binding, a significantly higher DAT selectivity was observed for [(18)F]FE@CIT. Hence, [(18)F]FE@CIT may be of interest for further clinical application.

No immunological benefit of selenium in consecutive patients with autoimmune thyroiditis.

BACKGROUND: Recently it has been demonstrated that after selenium (Se) supplementation in autoimmune thyroiditis (AIT) patients, there was a significant decrease of thyroid peroxidase (TPO) autoantibody (TPOAb) levels. The aim of our study was to evaluate the immunological benefit of Se administration in unselected AIT patients and thus address the question whether Se administration should generally be recommended for AIT patients. METHODS: Thirty-six consecutive AIT patients (aged 19-85 years) were included in the present study. In addition to their levothyroxine (LT(4)) treatment, 18 patients received 200 microg (2.53 micromol) sodium selenite per day orally for the time span of 3 months, whereas 18 patients received placebo. All patients had measurement of thyroid hormones, thyrotropin (TSH), autoantibodies (thyroglobulin antibodies [TgAb] and TPOAb), Se levels, and intracellular cytokine detection in CD4(+) and CD8(+) T cells of peripheral blood mononuclear cells (PBMC) by flow cytometry before and after Se or placebo administration. RESULTS: No significant difference in the TPOAb levels was found after Se administration (524 +/- 452 vs. 505 +/- 464 IU/mL; p > 0.05). Furthermore, we found no significant differences in the CD4(+) or CD8(+) cytokine pattern (IFN-gamma, IL-2, IL-4, IL-5, IL-6, IL-10, IL-13, TNF-alpha, TNF-beta) in patients before and after Se administration, in patients before and after placebo administration and between Se group and placebo group before and after Se vs. placebo administration. CONCLUSION: We demonstrate that Se administration in our AIT patient's cohort does not induce significant immunological changes, either in terms of cytokine production patterns of peripheral T lymphocytes or of TPOAb levels. Our data suggest that AIT patients with moderate disease activity (in terms of TPOAb and cytokine production patterns) may not (equally) benefit as patients with high disease activity.

Preparation and pre-vivo evaluation of no-carrier-added, carrier-added and cross-complexed [(68)Ga]-EDTMP formulations.

PURPOSE: The present study aimed to develop convenient preparation and quality control protocols for [(68)Ga]-EDTMP, a potential radiotracer for skeletal PET imaging. Furthermore, bone binding characteristics with special focus on the influence of carrier addition were evaluated. METHODS: No-carrier-added (nca), carrier-added and novel cross-complexed [(68)Ga]-EDTMP formulations were prepared using [(68)Ga]-gallium chloride and a commercial EDTMP kit. Respective bone binding characteristics were determined on the basis of an established in-vitro method using hydroxyapatite and human bone powders as binding matrices. RESULTS: Pre-vivo evaluation of nca [(68)Ga]-EDTMP yielded irreversible binding on the mineral bone phase characterised by fast binding kinetics. Generally, nca [(68)Ga]-EDTMP showed low uptake values comparable to nca [(99m)Tc]-EDTMP. Interestingly, the bone binding affinity of [(68)Ga]-EDTMP could be increased by the addition of carriers, presumably by changing the complex structure. CONCLUSIONS: This fast and reliable preparation protocol could enable small PET facilities without onsite cyclotron to perform PET bone scans. A comparison of all cross-complexed [(68)Ga]-EDTMP preparations further strengthens the recently presented "foreign carrier theory", which highlights carrier addition as a factor strongly affecting bone uptake of radiolabelled polyphosphonates. The clinical applicability of [(68)Ga]-EDTMP - particularly with respect to lesion specificity and sensitivity - should be clarified in forthcoming in-vivo studies.

[18F]FDG-PET/CT and MRI for initial pelvic lymph node staging in patients with cervical carcinoma: The potential usefulness of [18F]FDG-PET/MRI.

The current study aimed to determine the optimum diagnostic imaging technique out of magnetic resonance imaging (MRI), 18F-fludeoxyglucose positron emission tomography/computed tomography ([18F]FDG-PET/CT, otherwise known as PET/CT) and [18F]FDG-PET/MRI (otherwise known as PET/MRI) for the pelvic lymph node staging (N-staging) of untreated cervical carcinoma (CC). A total of 27 patients were included in the present study. All patients had undergone pre-treatment with PET/CT and MRI ≤45 days prior to undergoing a lymphadenectomy. The results from PET (separated from PET/CT), MRI and the statistically combined results of (virtual) PET/MRI were compared to those from histological analyses (the gold standard). A per-patient-based analysis of the detection of pelvic lymph node metastases indicated that PET/MRI had a sensitivity of 64%. The specificity of PET/CT and MRI were 69 and 62%, respectively. The positive predictive value (PPV) was 69 and 64% for PET/CT and MRI, respectively. The negative predictive value (NPV) was 64 and 62% for PET/CT and MRI, respectively. The sensitivity of the PET-guided PET/MRI and the MRI-guided PET/MRI was 64% for both. The specificity of the PET-guided PET/MRI and the MRI-guided PET/MRI was 77 and 62%, respectively. The PPV was 75% for PET-guided PET/MRI and 64% for MRI-guided PET/MRI, and the NPV was 67 and 62%, respectively. PET/CT and the virtual PET/MRI exhibited the same low sensitivity (64%). PET/MRI exhibited slightly better results than PET/CT regarding specificity (77 vs. 69%, respectively), PPV (75 vs. 69%, respectively) and NPV (67 vs. 64%, respectively). The results of the present study suggested that PET/CT and MRI are not optimal diagnostic modalities, and that PET/MRI does not necessarily lead to better results than PET/CT, in the pelvic N-staging of CC.

Higher serotonin transporter occupancy after multiple dose administration of escitalopram compared to citalopram: an [123I]ADAM SPECT study.

OBJECTIVES: Previous studies have investigated the occupancy of the serotonin reuptake transporter (SERT) after clinical doses of citalopram and other selective serotonin reuptake inhibitors. In the present study, the occupancies of SERT after multiple doses of escitalopram and citalopram were compared using the radioligand [(123)I]ADAM and single photon emission computed tomography (SPECT). METHODS: Fifteen healthy subjects received escitalopram 10 mg/day (n = 6) or citalopram 20 mg/day (n = 9) for a total of 10 days. SERT occupancies in midbrain were determined with SPECT and [(123)I]ADAM at three different time points: at baseline (no medication) and at 6 and 54 h after last drug intake. RESULTS: At 6 h after the last dose, mean SERT occupancies were 81.5 +/- 5.4% (mean+/-SD) for escitalopram and 64.0 +/- 12.7% for citalopram (p < 0.01). At 54 h after the last dose, mean SERT occupancies were 63.3 +/- 12.1% for escitalopram and 49.0 +/- 11.7% for citalopram (p < 0.05). The plasma concentrations of the S-enantiomer were of the same magnitude in both substances. For both drugs, the elimination rate of the S-enantiomer in plasma was markedly higher than the occupancy decline rate in the midbrain. CONCLUSION: The significantly higher occupancy of SERT after multiple doses of escitalopram compared to citalopram indicates an increased inhibition of SERT by escitalopram. The results can also be explained by an attenuating effect of R-citalopram on the occupancy of S-citalopram at the SERT.

Striatal D(2) receptor occupancy in bipolar patients treated with olanzapine.

We explored the relationship between striatal dopamine-2 (D(2)) receptor occupancy and extra-pyramidal symptoms (EPS) in bipolar patients receiving olanzapine. Seventeen patients with a DSM-IV diagnosis of bipolar disorder were treated with 5-45 mg/day olanzapine for at least 14 days. After that period, D(2) receptor occupancy was determined using Iodobenzamide (IBZM) and SPECT. EPS were assessed by the Simpson-Angus Scale (SAS) and Barnes-Akathisia Scale (BAS). We found a dose-dependent increase in occupancy: 5 mg led to 28-50%, 10 mg to 40-68%, 15 mg to 69%, 20 mg to 57-66%, 30 mg to 66% and 45 mg to 80% D(2) receptor occupancy; and a significant correlation between plasma levels and occupancy (R(2)=.55, P=.001). Similar to schizophrenic patients, bipolar patients did not exhibit EPS at D(2) occupancy levels of 28 to 80%. Although we did not find an increased vulnerability for acute EPS in bipolar patients receiving olanzapine at clinical relevant doses, this needs to be replicated with larger sample sizes.

Pre vivo, ex vivo and in vivo evaluations of [68Ga]-EDTMP.

INTRODUCTION: The objectives of this study were to develop a simple preparation method for [68Ga]-EDTMP and to evaluate the applicability of [68Ga]-EDTMP as a potential positron emission tomography (PET) bone imaging agent using pre vivo, ex vivo and in vivo models. METHODS: [68Ga]-EDTMP was prepared using 68Ga]-gallium chloride eluted from the 68Ge/68Ga generator and commercially available Multibone kits. Binding affinity to bone compartments was evaluated using a recently established pre vivo model. In vivo (microPET) and ex vivo experiments were performed in mice, and the results of which were compared with those obtained with [18F]-fluoride. RESULTS: [68Ga]-EDTMP was accessible via simple kit preparation and predominantly accumulated in bone tissue in vivo, ex vivo and pre vivo. Binding to mineral bone was irreversible, and low binding was observed in organic bone. In vivo microPET evaluation revealed predominant uptake in bone with renal excretion. Compared with [18F]-fluoride, the uptake was lower and the PET image quality was reduced. CONCLUSIONS: From the present evaluation, apart from the autonomy for PET centers without an onsite cyclotron, the advantage of [68Ga]-EDTMP over [18F]-fluoride is not apparent and the future clinical prospect of [68Ga]-EDTMP remains speculative.

18F fluoroethylations: different strategies for the rapid translation of 11C-methylated radiotracers.

INTRODUCTION: The translation of 11C-labeled compounds into their respective 18F-labeled derivatives is an important tool in the rapid development of positron emission tomography (PET) tracers. Thus, our aim was the development of a general method for the preparation of 18F-fluoroethylated compounds that (a) is applicable to a variety of precursors, (b) can be performed in a fully automated commercially available synthesizer and (c) enables this rapid translation of 11C-methylated tracers into their 18F-fluoroethylated analogs sharing the same precursor molecules. METHODS: Ten methods for the preparation and purification of different 18F-fluoroethylating agents were compared. Subsequently, five 18F-labeled PET tracers were synthesized under fully automated conditions. RESULTS: Radiochemical yields ranged from 34.4% to 60.8%, and time consumption ranged from 20 to 55 min for all methods. Use of 1-bromo-2-[18F]fluoroethane and distillation evinced as the method of choice. CONCLUSIONS: We were able to develop a general method for the preparation of a variety of 18F-fluoroethylated molecules. The provided tool is solely based on commercially available resources and has the potential to simplify and accelerate innovative PET tracer development in the future.

Vascular endothelial growth factor in thyroid cyst fluids.

BACKGROUND: The pathogenesis of cystic thyroid nodules is incompletely understood. Based on the assumption that vascular endothelial growth factor (VEGF) may play an important role in the pathogenesis of thyroid cyst fluid, we investigated the VEGF concentration in cyst fluids of thyroid lesions. DESIGN: Cyst fluids from 24 patients (age 31-84 years) were obtained using ultrasound-guided fine-needle aspiration. The patients' cystic thyroid nodules were of different origins. METHODS: Thyroid and cyst volumes were determined using high-resolution ultrasonography. VEGF concentrations were determined using a solid-phase enzyme-linked immunosorbent assay (ELISA). RESULTS: Differing elevated VEGF concentrations were demonstrated in cyst fluids of thyroid nodules of varied origins. The VEGF concentration in cyst fluid of patients with adenomatous goiter was significantly higher (P < 0.05) than that in thyroid nodules with cystic degeneration. The highest level of VEGF was found in bloody cyst fluid when compared with levels in other cyst fluids (P < 0.05). Interestingly, there was significant correlation (P < 0.01) between thyroid volume and VEGF concentration in cyst fluid, but no significant correlation (P = 0.20) between cyst volume and VEGF concentration. CONCLUSION: Significantly increased VEGF concentrations were found in bloody cyst fluid and in cyst fluid of thyroid adenomatous goiter, compared with VEGF concentrations in degenerative thyroid cysts. Our results suggest that VEGF may play an important role in the pathogenesis of thyroid cyst fluid.

A positron emission tomography microdosing study with a potential antiamyloid drug in healthy volunteers and patients with Alzheimer's disease.

This work describes a microdosing study with an investigational, carbon 11-labeled antiamyloid drug, 1,1'-methylene-di-(2-naphthol) (ST1859), and positron emission tomography (PET) in healthy volunteers (n = 3) and patients with Alzheimer's disease (n = 6). The study aimed to assess the distribution and local tissue pharmacokinetics of the study drug in its target organ, the human brain. Before PET studies were performed in humans, the toxicologic characteristics of ST1859 were investigated by an extended single-dose toxicity study according to guidelines of the Food and Drug Administration and European Medicines Agency, which are relevant for clinical trials with a single microdose. After intravenous bolus injection of 341 +/- 21 MBq [(11)C]ST1859 (containing <11.4 nmol of unlabeled ST1859), peripheral metabolism was rapid, with less than 20% of total plasma radioactivity being in the form of unchanged parent drug at 10 minutes after administration. In both the control and patient groups, uptake of radioactivity into the brain was relatively fast (time to reach maximum concentration, 9-17 minutes) and pronounced (maximum concentration [standardized uptake value], 1.3-2.2). In both healthy volunteers and patients, there was a rather uniform distribution of radioactivity in the brain, including both amyloid-beta-rich and -poor regions, with slow washout of radioactivity (half-life, 82-185 minutes). In conclusion, these data provide important information on the blood-brain barrier penetration and metabolism of an investigational antiamyloid drug and suggest that the PET microdosing approach is a useful method to describe the target-organ pharmacokinetics of radiolabeled drugs in humans.

In vitro evaluation of no carrier added, carrier added and cross-complexed [90Y]-EDTMP provides evidence for a novel "foreign carrier theory".

The present study focused on the preparation of novel bone tracers containing yttrium as radionuclide or carrier. Moreover, these preparations were comparatively evaluated in vitro on the basis of a recently presented pre vivo model comprising binding studies on synthetic and human bone powder. It was shown that among the therapeutic radionuclides, no carrier added [(90)Y]-EDTMP exceeded [(188)Re]-EDTMP while yielding lower binding values than [(153)Sm]-EDTMP. Furthermore, the authors investigated the influence of "foreign" carriers added to [(90)Y]-EDTMP, [(99m)Tc]-EDTMP and [(111)In]-EDTMP by the method of cross-complexation. The findings reveal a new paradigm: a carrier more foreign to the complexed radionuclide causes a higher binding increase on human bone matrices in vitro than a more "related" carrier.

T lymphocyte cytokine production patterns in hashimoto patients with elevated calcitonin levels and their relationship to tumor initiation.

The aim of the study was to evaluate the possible changes in CD4+ and CD8+ T-cell cytokine production patterns in Hashimoto's thyroiditis (HT) with elevated calcitonin (CT). Fourteen consecutive patients with verified HT were included in the present study. Patients were divided into two groups. Group I: 7 HT patients with elevated CT levels (>10 pg/ml); Group II: 7 HT patients with CT levels <10 pg/ml). All patients underwent intracellular cytokine detection in CD4+ and CD8+ T-cells of peripheral blood mononuclear cells (PBMC) by flow cytometry. Patients with elevated CT levels (group I) had significantly higher percentages of CD8+ cells producing IFN-gamma compared to healthy donors. A detailed analysis of cytokine production patterns revealed that this was accompanied by an increased frequency of single IFN-gamma positive cells, i.e., cells not expressing most of the other cytokines tested. Similarly, patients in group I also showed higher percentages of CD8+ TNF-alpha positive cells than healthy donors. In this case, cells co-expressing TNF-alpha and IFN-gamma were found at significantly higher frequencies. No increase in Th1 type cytokines, such as IFN-gamma or TNF-alpha, was detectable in CD4+ T-cells. In contrast, CD4+ T-cells from group I patients showed significantly higher percentages of cells producing Th2 cytokines, such as IL-4 or IL-13. The lack of increased Th1 cytokine production accompanied by an increased Th2 cytokine production seems to be a special feature of HT patients with elevated CT levels that may reflect a pathogenetic mechanism for tumor initiation.

Calcitonin measurements for early detection of medullary thyroid carcinoma or its premalignant conditions in Hashimoto's thyroiditis.

The measurement of basal serum calcitonin (CT) in patients with evidence of Hashimoto's thyroiditis (HT) has been proposed in a recent study demonstrating an increased prevalence of elevated basal and stimulated CT. The aim of this study was to evaluate the frequency and relevance of elevated CT levels in HT. The basal sera CT were measured in 568 consecutive HT patients using a chemiluminescent immuno-assay. Whenever the serum CT was > 10 pg/ml, a pentagastrin (PG) stimulation test was performed. Two patients with abnormal/pathological PG tests were identified. Total thyroidectomy and lymph node dissection revealed for the first patient medullary thyroid carcinoma (MTC) and for the second patient C cell hyperplasia (CCH), together with papillary thyroid carcinoma. Our data showed a low prevalence of MTC and its premalignant condition CCH in HT patients; nevertheless, the patient with MTC presented lymph node metastasis. The fact that both cases presented without evidence of nodular thyroid disease highlights the persistent diagnostic dilemma of CT screening programs.

NCA nucleophilic radiofluorination on substituted benzaldehydes for the preparation of [18F]fluorinated aromatic amino acids.

Nucleophilic aromatic substitution is a challenging task in radiochemistry. Therefore, a thorough evaluation and optimisation of this step is needed to provide a satisfactory tool for the routine preparation of [(18)F]fluorinated aromatic amino acids. Two methods, already proposed elsewhere, were evaluated and improved. The yields for the radiofluorination were increased whereas activity loss during solid phase extraction was observed. Radiochemical yields for the two methods were 92.7+/-5.5% (method 1) and 92.1+/-12.3% (method 2) for conversion and 11.1+/-2.8% (method 1) and 34.8+/-0.6% (method 2) for purification, respectively. In total, we demonstrate an optimised method for the preparation of this important class of [(18)F]fluorinated synthons for PET.

[Evaluation of the performance of a gamma camera equipped with a 5/8" versus 1" thick NaI detector]. / Vergleich der Abbildungseigenschaften einer Gammakamera mit 5/8" (15 mm) NaI-Szintillationskristall und 1" (25 mm)-Kristall.

The upgrade of a gamma camera from a 5/8" to a 1" thick crystal, the latter with StarBrite technology, prompted to the investigation of changes in performance parameters for planar scintigraphy and SPECT as well as for PET in coincidence mode. For planar and SPECT parameters, the performance was measured according to NEMA Standard Protocol NU1-2001. No changes were found in terms of intrinsic uniformity, intrinsic spatial resolution, linearity, energy resolution, system resolution, and tomographic system resolution. The only change was an increase of system sensitivity for higher energy gamma rays. For the PET scanner in coincidence mode, the image quality of the camera was determined according to NEMA NU2-2001. Visually and in terms of contrast values there was a significant improvement of image quality. Changes in image quality relevant for clinical use were tested by evaluation of planar patient scans acquired within a short time with two gamma cameras of the same type, different only in crystal thickness (5/8" and 1"). No statistically significant difference was found between corresponding scans. For planar and SPECT imaging, the gamma camera with 1" thick detector and StarBrite technology demonstrated the same performance of a camera with a 5/8" crystal. For PET in coincidence mode the new detector proved clearly superior.

Clinical Value of 18F-fluorodihydroxyphenylalanine Positron Emission Tomography/Contrast-enhanced Computed Tomography (18F-DOPA PET/CT) in Patients with Suspected Paraganglioma.

AIM: To evaluate (18)F-fluorodihydroxyphenylalanine-positron emission tomography/ contrast-enhanced computed tomography ((18)F-DOPA PET/CT) for the detection of paragangliomas (PARA) without any patient selection, such as genetic predisposition for the development of these tumors, history of metastatic PARA or hormonal status. PATIENTS AND METHODS: In this retrospective study, 28 consecutive patients (15 women, 13 men; mean age=46.4 years; age range=19-73 years), who were referred to our PET/CT center for the detection of clinically suspected PARA, were included. Final diagnosis was confirmed by histological reports of surgically proven lesions and/or clinical follow-up (including laboratory results and/or PET/CT follow-up). RESULTS: On a per-lesion basis (45 lesions) analysis, there was a sensitivity of 64.3% for CT, 73.8% for PET, 100% for PET/CT and a positive predictive value (PPV) of 93.1% for CT, 96.9% for PET and 100% for PET/CT. On a per-patient basis analysis, the sensitivity, specificity and accuracy for CT was 86.7%, 84.6% and 85.7%, respectively, and, for PET 80%, 100% and 89.3%, respectively, and, for PET/CT 100%. CONCLUSION: Based on our data, (18)F-DOPA PET/CT is a "one-stop diagnostic modality" for the assessment of patients with suspected PARA.

Influence of functional haplotypes in the drug transporter gene ABCB1 on central nervous system drug distribution in humans.

BACKGROUND AND OBJECTIVE: Single nucleotide polymorphisms in the human multidrug-resistance gene ABCB1 have been reported to be associated with altered expression and function of P-glycoprotein, an efflux transporter, expressed at the blood-brain barrier. To test whether certain ABCB1 haplotypes contribute to interindividual differences in central nervous system drug distribution, brain distribution of a model P-glycoprotein substrate, the calcium channel inhibitor verapamil, was measured by positron emission tomography (PET) in 2 groups of healthy volunteers. METHODS: Ten homozygous carriers (cases) of the TTT haplotype (3435T, 1236T, and 2677T) and 10 controls homozygous for the wild-type CGC haplotype (3435C, 2677G, and 1236C) were administered a mean intravenous bolus of 412 +/- 114 MBq carbon 11-labeled verapamil containing less than 15 nmol of unlabeled verapamil. PET imaging of brain tissue and venous blood sampling were performed for 1 hour after dosing. RESULTS: As a measure of brain penetration, the ratio of PET area under the time-radioactivity curve (AUC) to plasma AUC was calculated from time-radioactivity curves, with a mean ratio of 1.1 +/- 0.3 (SD) (95% confidence interval, 0.9-1.3) for cases and 1.1 +/- 0.2 (95% confidence interval, 0.9-1.2) for controls, respectively (P = .96). Mean brain AUC values were 31.2 +/- 3.9 and 35.7 +/- 5.7 for the TTT and CGC haplotype, respectively (P = .11). Plasma AUCs were not significantly different. CONCLUSION: No difference in the brain distribution of [(11)C]verapamil could be detected in healthy volunteers differing in ABCB1 haplotypes.