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Fireballs of liquid organic peroxides differ from those of liquid hydrocarbon fuels. Modified equations for predicting the fireball diameter, height, surface emissive power and the duration in dependence of the fuel mass are presented for di-tert-butyl peroxide. They base on 13 steel drum tests with fuel masses from 10 kg to 168 kg. Moreover, computational fluid dynamics simulations are performed using the laminar flamelet approach and a statistically turbulence treatment. Fireballs involving peroxide from 10 kg to 80 kg were simulated and their properties compared to the experimentally developed models. The deviations of each property are partially compensating each other leading to an adequate prediction of thermal safety distances for both, a time-independent and a time-averaged treatment. Simulations prove to be a good tool for predicting thermal radiation hazards of fireball scenarios., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Introduction: (-)-[(18)F]Flubatine is a PET tracer with high affinity and selectivity for the nicotinic acetylcholine α4β2 receptor subtype. A clinical trial assessing the availability of this subtype of nAChRs was performed. From a total participant number of 21 Alzheimer's disease (AD) patients and 20 healthy controls (HCs), the following parameters were determined: plasma protein binding, metabolism and activity distribution between plasma and whole blood., Methods: Plasma protein binding and fraction of unchanged parent compound were assessed by ultracentrifugation and HPLC, respectively. The distribution of radioactivity (parent compound+metabolites) between plasma and whole blood was determined ex vivo at different time-points after injection by gamma counting after separation of whole blood by centrifugation into the cellular and non-cellular components. In additional experiments in vitro, tracer distribution between these blood components was assessed for up to 90min., Results: A fraction of 15%±2% of (-)-[(18)F]Flubatine was found to be bound to plasma proteins. Metabolic degradation of (-)-[(18)F]Flubatine was very low, resulting in almost 90% unchanged parent compound at 90min p.i. with no significant difference between AD and HC. The radioactivity distribution between plasma and whole blood changed in vivo only slightly over time from 0.82±0.03 at 3min p.i. to 0.87±0.03 at 270min p.i. indicating the contribution of only a small amount of metabolites. In vitro studies revealed that (-)-[(18)F]Flubatine was instantaneously distributed between cellular and non-cellular blood parts., Discussion: (-)-[(18)F]Flubatine exhibits very favourable characteristics for a PET radiotracer such as slow metabolic degradation and moderate plasma protein binding. Equilibrium of radioactivity distribution between plasma and whole blood is reached instantaneously and remains almost constant over time allowing both convenient sample handling and facilitated fractional blood volume contribution assessment., (Copyright © 2014 Elsevier Inc. All rights reserved.)

To develop a basis for the separation of a (18)F-labeled PET radiotracer from its nitro precursor, we performed an analytical HPLC study using the unlabeled reference compound and the corresponding nitro precursor. Aim of the study was to find a separation in which the fluoro derivative elutes in front of the nitro precursor with appropriate separation parameters. Several RP phases as well as a bare silica column were investigated with ACN and MeOH as organic modifiers and aqueous NH4OAc because of the basic character of the analytes. Four types of separation were observed based on different interaction mechanisms. When ACN/20mM NH4OAc aq. was used mainly cationic-exchange and hydrophobic interactions contributed to the retention. A reversal of elution order could be observed starting from 95% ACN and subsequent increasing of the water content. This phenomenon was observed for all RP phases and seems to be independent of the different spacers bound to the silica. By contrast, using MeOH/20mM NH4OAc aq. the elution order depends on the phase material. Two columns with the potential to perform π-π interactions showed different separation behavior compared to the other RP phases., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Introduction: Phosphopeptides represent interesting compounds to study and elucidate cellular protein phosphorylation/dephosphorylation processes underlying various signal transduction pathways. However, studies of phosphopeptide action in cells are severely constrained by the negatively charged phosphate moiety of the phosphopeptide resulting in poor transport through the cell membrane. The following study describes the synthesis and radiopharmacological evaluation of two (18)F-labeled phosphopeptide-cell-penetrating peptide dimers. The polo-like kinase-1-binding hexaphosphopeptide H-Met-Gln-Ser-pThr-Pro-Leu-OH was coupled to cell-penetrating peptides (CPPs), either sC18, a cathelicidin-derived peptide, or the human calcitonin derivative hCT(18-32)-k7., Methods: Radiolabeling was accomplished with the prosthetic group N-succinimidyl 4-[(18)F]fluorobenzoate ([(18)F]SFB) using both, conventional and microfluidic-based bioconjugation of [(18)F]SFB to N-terminal end of phosphopeptide part of the peptide dimers. Cellular uptake studies in human cancer cell lines HT-29 and FaDu cells at 4 °C and 37 °C and small animal PET in BALB/c mice were utilized for radiopharmacological characterization., Results: Isolated radiochemical yields ranged from 2% to 4% for conventional bioconjugation with [(18)F]SFB. Significantly improved isolated radiochemical yields of up to 26% were achieved using microfluidic technology. Cellular uptake studies of radiolabeled phosphopeptide and phosphopeptide-CPP dimers indicate enhanced internalization of 50% ID/mg protein after 2 h for both phosphopeptide dimers compared to the phosphopeptide alone (<1% ID/mg protein). In vivo biodistribution of (18)F-labeled peptide dimers was determined with small animal PET revealing a superior biodistribution pattern of sC18-containing peptide dimer MQSpTPL-sC18 [(18)F]4., Conclusion: ([18)F]SFB labeling of the phosphopeptide-CPP dimers using a microfluidic system leads to an improved chemoselectivity towards the N-terminal NH(2) group compared to the conventional labeling approach. Cell-penetrating peptide sC18 can be considered as an ideal molecular shuttle for intracellular delivery of the Plk1-PBD-binding hexaphosphopeptide as demonstrated by its favourable radiopharmacological profile., (Copyright © 2012 Elsevier Inc. All rights reserved.)

New macrocyclic 1,4,8,11-tetraazacyclotetradecane (cyclam) derivatives with 1, 2 and 4 neurotensin(8-13) units 4, 5 and 7 have been synthesized. Compounds 4 and 5 were prepared by the reaction of non-stabilized neurotensin(8-13) and cyclamtetrapropionic acid 2 using 1-ethyl-3-(3-dimethylaminocarbonyl)carbodiimide-hydrochloride and N-hydroxysulfosuccinimide. The tetrameric compound 7 was synthesized by Michael addition of neurotensin(8-13) acrylamide 6 and cyclam 1. The copper(II) complexation behavior of 4, 5 and 7 was investigated by UV/visible spectrophotometry and shows that the metal center resides inside the N4 chromophore with additional apical interactions established with pendant arms. The novel tetrabranched NT(8-13) cyclam 7 with nanomolar neurotensin receptor 1 binding affinity was efficiently radiolabeled with (64)Cu under mild conditions. (64)Cu⊂7 showed slow transchelation in the presence of a large amount of cyclam as competing ligand, while it completely remains intact in the presence of EDTA. The in vivo behavior of (64)Cu⊂7 was studied in rats and mice. The metabolic stability in rodent models was high with a half-life of intact (64)Cu⊂7 in plasma of 34 min in rats and 60 min in the mice, respectively. The binding affinity was high enough to demonstrate in vivo binding of (64)Cu⊂7 to NTR1 overexpressing HT-29 tumor xenotransplants in nude mice. Regarding elimination, (64)Cu⊂7 showed a substantial renal and reticuloendothelial accumulation. On the other hand, metabolization of the compound in vivo with a resulting metabolite-postulated to be the (64)Cu-cyclam-tetraarginine complex-also showed long retention in the circulating blood, preventing a better contrast of tumor imaging., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Different RP-HPLC columns (phenyl, conventional ODS, cross-linked C(18) and special end-capped C(8) and C(18) phases) were used to investigate the separation of four basic ionizable isomers. Using ACN/20mM NH(4)OAc aq., a separation was observed exclusively on RP columns with higher silanol activity at unusual high ACN concentration, indicating cation-exchange as main retention mechanism. Using MeOH/20mM NH(4)OAc aq., another separation at low MeOH concentrations was observed on both, RP columns with higher as well as RP columns with lower silanol activity, which is mainly based on hydrophobic interactions. The isomers were also separated on a bare silica column at higher MeOH content using NH(4)OAc. Since cation-exchange governs this retention, the elution order was different compared to the RP phases. A strong retention on the silica column was observed in ACN, which could be attributed to partition processes as additional retention mechanism., (Copyright © 2010 Elsevier B.V. All rights reserved.)

A new azido derivative of 2,2'-dipicolylamine (Dpa), 2-azido-N,N-bis((pyridin-2-yl)methyl)ethanamine, (Dpa-N(3)) was readily prepared from the known 2-(bis(pyridin-2-ylmethyl)amino)ethanol (Dpa-OH). It was demonstrated that Dpa-N(3) could be efficiently labeled with both [Re(CO)(3)(H(2)O)(3)]Br and [(99m)Tc(H(2)O)(3)(CO)(3)](+) to give [Re(CO)(3)(Dpa-N(3))]Br and [(99m)Tc(CO)(3)(Dpa-N(3))](+), respectively. Furthermore, Dpa-N(3) was successfully coupled, on the solid phase, to a Peptide Nucleic Acid (PNA) oligomer (H-4-pentynoic acid-spacer-spacer-tgca-tgca-tgca-Lys-NH(2); spacer= -NH-(CH(2))(2)-O-(CH(2))(2)-O-CH(2)-CO-) using the Cu(I)-catalyzed [2+3] azide/alkyne cycloaddition (Cu-AAC, often referred to as the prototypical "click" reaction) to give the Dpa-PNA oligomer. Subsequent labeling of Dpa-PNA with [(99m)Tc(H(2)O)(3)(CO)(3)](+) afforded [(99m)Tc(CO)(3)(Dpa-PNA)] in radiochemical yields >90%. Partitioning experiments in a 1-octanol/water system were carried out to get more insight on the lipophilicity of [(99m)Tc(CO)(3)(Dpa-N(3))](+) and [(99m)Tc(CO)(3)(Dpa-PNA)]. Both compounds were found rather hydrophilic (log D(o/w) values at pH=7.4 are -0.50: [(99m)Tc(CO)(3)(Dpa-N(3))](+) and -0.85: [(99m)Tc(CO)(3)(Dpa-PNA)]. Biodistribution studies of [(99m)Tc(CO)(3)(Dpa-PNA)] in Wistar rats showed a very fast blood clearance (0.26 ± 0.1 SUV, 1h p.i.) and modest accumulation in the kidneys (5.45 ± 0.45 SUV, 1h p.i.). There was no significant activity in the thyroid and the stomach, demonstrating a high in vivo stability of the (99m)Tc-labeled Dpa-PNA conjugate., (Copyright © 2010 Elsevier Inc. All rights reserved.)

High-performance liquid chromatography enantioseparation of vesamicol and six novel azaspirovesamicols (amino alcohols) was accomplished on different chiral stationary phases (CSPs) by using an optical rotation based chiral detector for identification of the resolved enantiomers. The Pirkle-type column Reprosil Chiral-NR was found to be most suitable for chiral resolution in normal phase (NP) mode; all compounds could be enantioseparated successfully. Also the cellulose-based column Reprosil Chiral-OM showed appropriate separation properties by using NP conditions. The amylose-type column Reprosil Chiral-AM-RP was most suitable for enantioseparation in reversed phase (RP) mode; five out of seven compounds were resolved. This CSP showed a considerably higher capability for chiral recognition of vesamicol derivatives in RP mode than the corresponding cellulose-based column Reprosil Chiral-OM-RP. Enantioseparation with the teicoplanin aglycone-based column Reprosil Chiral-AA was successful under polar ionic mobile phase conditions., (Copyright 2010 Elsevier B.V. All rights reserved.)

Increased plasma levels of S100 proteins and interaction of S100 proteins with receptor for advanced glycation end products (RAGE) have been associated with a number of disease states, including chronic inflammatory processes and atherosclerosis. However, data concerning the role of circulating S100 proteins in these pathologies in vivo are scarce and, furthermore, it is currently not known whether RAGE is the sole receptor for extracellular S100 proteins in vivo. We report a novel methodology using recombinant human S100 proteins radiolabelled with fluorine-18, particularly, (18)F-S100A12, in receptor binding studies and cellular association studies in vitro, and in dynamic small animal positron emission tomography (PET) studies in rats in vivo. Association to both human aortic endothelial cells and macrophages revealed specific binding of (18)F-S100A12 to RAGE, but, furthermore, provides evidence for interaction of (18)F-S100A12 to various scavenger receptors (SR). PET data showed temporary association of (18)F-S100A12 with tissues overexpressing RAGE (e.g., lung), and, moreover, accumulation of (18)F-S100A12 in tissues enriched in cells overexpressing SR (e.g., liver and spleen). Blockade of overall SR interaction by maleylated BSA (malBSA) clearly shows diminished in vivo association of (18)F-S100A12 to these tissues as well as a significant increment of the mean plasma residence time of (18)F-S100A12 (4.8+/-0.4 h vs. 2.3+/-0.3 h). The present approach first demonstrates that besides RAGE also scavenger receptors contribute to distribution, tissue association and elimination of circulating proinflammatory S100A12., (2009 Elsevier Ltd. All rights reserved.)

Phenylpiperidinyl-octahydro-benzo[1,4]oxazines represent a new class of conformationally restrained vesamicol analogues. Derived from this morpholine-fused vesamicol structure, a new fluorine-18-labeled 4-fluorobenzoyl derivative ([(18)F]FBMV) was synthesized with an average specific activity of 75 GBq/micromol and a radiochemical purity of 99%. The radiolabeling method included an exchange reaction of a 4-nitro group of the precursor by fluorine-18, a reduction procedure to eliminate excess of the nitro compound, followed by a high-performance liquid chromatography purification. [(18)F]FBMV demonstrates (i) a moderate lipophilic character with a logD(pH7.0) 1.8+/-0.10; (ii) a considerable binding affinity to the vesicular acetylcholine transporter (VAChT) (K(i)=27.5 nM), as determined using PC12 cells transfected with a VAChT cDNA, and a low affinity to sigma(1,2) receptors (K(i) >3000 nM); (iii) a good uptake into the rat and pig brains; (iv) a typical accumulation in the VAChT-containing brain regions; and (v) an approximately 20% reduction in cortical tracer binding after a specific cholinergic lesion using 192IgG-saporin. [(18)F]FBMV exhibits another PET marker within the group of vesamicol derivatives that demonstrates potentials in imaging brain cholinergic deficits, while its usefulness in clinical practice must await further investigation.

Cholinergic neurotransmission depends on the integrity of nicotinic acetylcholine receptors (nAChRs), and impairment of both is characteristic for various neurodegenerative diseases. Visualization of specific receptor subtypes by positron emission tomography (PET) has potential to assist with diagnosis of such neurodegenerative diseases and with design of suitable therapeutic approaches. The goal of our study was to evaluate in vivo the potential of (18)F-labelled (+)- and (-)-norchloro-fluoro-homoepibatidine ([(18)F]NCFHEB) in comparison to 2-[(18)F]F-A-85380 as PET tracers. In the brains of NMRI mice, highest levels of radioactivity were detected at 20 min post-injection of (+)-[(18)F]NCFHEB, (-)-[(18)F]NCFHEB, and 2-F-[(18)F]-A-85380 (7.45, 5.60, and 3.2% ID/g tissue, respectively). No marked pharmacological adverse effects were observed at 25 mug NCFHEB/kg. Uptake studies in RBE4 cells and in situ perfusion studies suggest an interaction of epibatidine and NCFHEB with the carrier-mediated choline transport at the blood-brain barrier. The data indicate that (+)- and (-)-[(18)F]NCFHEB have potential for further development as PET tracers.

With the aim of producing selective radiotracers for in vivo imaging of the vesicular acetylcholine transporter (VAChT) using positron mission tomography (PET), here, we report synthesis and analysis of a new class of conformationally constrained vesamicol analogues with moderate lipophilicity. The sequential ring opening on trans-1,4-cyclohexadiene dioxide enabled an approach to synthesize 6-arylpiperidino-octahydrobenzo[1,4]oxazine-7-ols [morpholino vesamicols]. The radiosynthesis of the [18F]fluoroacetyl-substituted derivative ([18F]FAMV) was achieved starting from a corresponding bromo precursor [2-Bromo-1-[7-hydroxy-6-(4-phenyl-piperidin-1-yl)-octahydro-benzo[1,4]oxazin-4-yl]-ethanone] and using a modified commercial computer-controlled module system with a radiochemical yield of 27+/-4%, a high radiochemical purity (99%) and a specific activity of 35 GBq/micromol. In competitive binding assays using a PC12 cell line overexpressing VAChT and [3H]-(-) vesamicol, 2-fluoro-1-[7-hydroxy-6-(4-phenyl-piperidin-1-yl)-octahydro-benzo[1,4]oxazin-4-yl]-ethanone (FAMV) demonstrated a high selectivity for binding to VAChT (K(i): 39.9+/-5.9 nM) when compared to its binding to sigma 1/2 receptors (Ki>1500 nM). The compound showed a moderate lipophilicity (logD (pH 7)=1.9) and a plasma protein binding of 49%. The brain uptake of [18F]FAMV was about 0.1% injected dose per gram at 5 min after injection and decreased continuously with time. Notably, an increasing accumulation of radioactivity in the lateral brain ventricles was observed. After 1 h, the accumulation of [18F]FAMV, expressed as ratio to the cerebellum, was 4.5 for the striatum, 2.0 for the cortical and 1.5 for the hippocampal regions, measured on brain slices using ex vivo autoradiography. At the present time, 75% of [18F]FAMV in the plasma was shown to be metabolized to various hydrophilic compounds, as detected by high-performance liquid chromatography. The degradation of [18F]FAMV was also detected in brain extracts as early as 15 min post injection (p.i.) and increased to 50% at 1 h postinjection. In conclusion, although the chemical properties of [18F]FAMV and the selectivity of binding to VAChT appear to be promising indicators of a useful PET tracer for imaging VAChT, a low brain extraction, in combination with only moderate specific accumulation in cholinergic brain regions and an insufficient in vivo stability prevents the application of this compound for neuroimaging in humans.

Introduction: Gamma amino butyric acid type A (GABA(A)) receptors are involved in a variety of neurological and psychiatric diseases, which have promoted the development and use of radiotracers for positron emission tomography imaging. Radiolabeled benzodiazepine antagonists such as flumazenil have most extensively been used for this purpose so far. Recently, the non-benzodiazepine pyrazolopyrimidine derivative indiplon with higher specificity for the alpha(1) subtype of the GABA(A) receptor has been introduced for treatment of insomnia. The aim of this study was the development and biological evaluation of an (18)F-labeled derivative of indiplon., Methods: Both [(18)F]fluoro-indiplon and its labeling precursor were synthesized by two-step procedures starting from indiplon. The radiosynthesis of [(18)F]fluoro-indiplon was performed using the bromoacetyl precursor followed by multiple-stage purification using semipreparative HPLC and solid phase extraction. Stability, partition coefficients, binding affinities and regional brain binding were determined in vitro. Biodistribution and radiotracer metabolism were studied in vivo., Results: [(18)F]Fluoro-indiplon was readily accessible in good yields (38-43%), with high purity and high specific radioactivity (>150 GBq/micromol). It displays high in vitro stability and moderate lipophilicity. [(18)F]Fluoro-indiplon has an affinity to GABA(A) receptors comparable to indiplon (K(i)=8.0 nM vs. 3.4 nM). In vitro autoradiography indicates high [(18)F]fluoro-indiplon binding in regions with high densities of GABA(A) receptors. However, ex vivo autoradiography and organ distribution studies show no evidence of specific binding of [(18)F]fluoro-indiplon. Furthermore, the radiotracer is rapidly metabolized with high accumulation of labeled metabolites in the brain., Conclusions: Although [(18)F]fluoro-indiplon shows good in vitro features, it is not suitable for in vivo imaging studies because of its metabolism. Structural modifications are needed to develop derivatives with higher in vivo stability.

N,N-Dimethyl-2-(2-amino-4-methylthiophenylthio)benzylamine (SMe-ADAM, 1) is a highly potent and selective inhibitor of the serotonin transporter (SERT). This compound was labeled with carbon-11 by methylation of the S-desmethyl precursor 10 with [(11)C]methyl iodide to obtain the potential positron emission tomography (PET) radioligand [(11)C]SMe-ADAM. The radiochemical yield was 27 +/- 5%, and the specific radioactivity was 26-40 GBq/micromol at the end of synthesis. Ex vivo and in vivo biodistribution experiments in rats demonstrated a rapid accumulation of the radiotracer in brain regions known to be rich in SERT, such as the thalamus/hypothalamus region (3.59 +/- 0.41%ID/g at 5 min after injection). The specific uptake reached a thalamus to cerebellum ratio of 6.74 +/- 0.95 at 60 min postinjection. The [(11)C]SMe-ADAM uptake in the thalamus was significantly decreased by pretreatment with fluoxetine to 38 +/- 11% of the control value. Furthermore, no metabolites of [(11)C]SMe-ADAM could be detected in the SERT-rich regions of the rat brain. It is concluded that [(11)C]SMe-ADAM may be a suitable PET ligand for SERT imaging in the living brain.

The subtype-specificity of newly synthesised epibatidine-related compounds, norchloro-fluoro-homoepibatidine (NCFHEB) and derivatives, to neuronal nicotinic acetylcholine receptors (nAChR) has been investigated. NCFHEBs were assayed in competitive binding assays to (+/-)-[(3)H]epibatidine-labelled rat thalamic nAChRs and human alpha4beta2, alpha3beta4, and alpha7 nAChRs, expressed in stably transfected HEK-293 and SH-SY5Y cells. The binding affinity of (+)-NCFHEB (K(i): 0.064 nM) and (-)-NCFHEB (K(i): 0.112 nM) to human alpha4beta2 nAChR is in the same order of magnitude as that of epibatidine (K(i): 0.014 nM). However, because the affinity of both NCFHEB-enantiomers to human alpha3beta4 nAChR is up to 65 times lower than that of epibatidine, the alpha4beta2 subtype-specificity of NCFHEB is increased up to 1,400% compared to epibatidine.

The explosive properties of mixtures of aqueous hydrogen peroxide (H(2)O(2)) and different alcohols (R-OH) like 2-propanol (2-PropOH), 2-methyl-2-propanol (TBA), 2-methyl-2-butanol (TAA) and 2-methyl-2-pentanol (THA) were investigated. Among others, the potential hazard of such mixtures may be characterized by their ability to react by different mechanisms of an explosion in the condensed phase, e.g. the thermal explosion or the detonation. Accordingly, the mixtures were experimentally investigated either by heating them up under confinement in different autoclaves or by exposing them to a shock wave impact applying the steel tube test. The results are discussed and compared to literature data.

5alpha-Cyprinol sulfate was isolated from bile of the Asiatic carp, Cyprinus carpio. 5alpha-Cyprinol sulfate was surface active and formed micelles; its critical micellization concentration (CMC) in 0.15 M Na+ using the maximum bubble pressure device was 1.5 mM; by dye solubilization, its CMC was approximately 4 mM. At concentrations >1 mM, 5alpha-cyprinol sulfate solubilized monooleylglycerol efficiently (2.1 molecules per mol micellar bile salt). When infused intravenously into the anesthetized rat, 5alpha-cyprinol sulfate was hemolytic, cholestatic, and toxic. In the isolated rat liver, it underwent little biotransformation and was poorly transported (Tmax congruent with 0.5 micromol/min/kg) as compared with taurocholate. 5alpha-Cyprinol, its bile alcohol moiety, was oxidized to its corresponding C27 bile acid and to allocholic acid (the latter was then conjugated with taurine); these metabolites were efficiently transported. 5alpha-Cyprinol sulfate inhibited taurocholate uptake in COS-7 cells transfected with rat asbt, the apical bile salt transporter of the ileal enterocyte. 5alpha-Cyprinol had limited aqueous solubility (0.3 mM) and was poorly absorbed from the perfused rat jejunum or ileum. Sampling of carp intestinal content indicated that 5alpha-cyprinol sulfate was present at micellar concentrations, and that it did not undergo hydrolysis during intestinal transit. These studies indicate that 5alpha-cyprinol sulfate is an excellent digestive detergent and suggest that a micellar phase is present during digestion in cyprinid fish.

A modified method for the synthesis of the intermediate product N-Boc-3,4-di(Boc-O)-6-iodo-L-phenylalanine ethyl ester of the [18F]FDOPA precursor preparation was developed. With the application of bis-(trifluoroacetoxy)-iodobenzene for the iodination step with elemental iodine the yield of the intermediate can be increased from 12% to 50-60%. By replacing silica-gel-based RP HPLC column by a polymer-based column for semi-preparative purification of [18F]FDOPA from the reaction mixture the radiochemical purity of the final product can be increased up to >99%. For the determination of the radiochemical impurity [18F]fluoride a HPLC method using a column with polymer-based RP material was introduced.

The present study describes the synthesis of the [18F]fluoromethyl analogue of (+)-McN5652 ([18F]FMe-McN) as a new potential tracer for the serotonin transporter. In vitro binding studies have shown that FMe-McN displays only slightly lower affinity for the serotonin transporter (K(i) = 2.3 +/- 0.1 nM) than (+)-McN5652 (K(i) = 0.72 +/- 0.2 nM). The radiofluorinated tracer [18F]FMe-McN was prepared by reaction of normethyl (+)-McN5652 with the fluoromethylation agent [18F]bromofluoromethane in an overall radiochemical yield of 5 +/- 1% (decay-corrected, related to [18F]fluoride) and with high specific radioactivity (200-2,000 GBq/micromol at the end of synthesis).

The usefulness of 18F-labelled carbohydrates, especially 2-deoxy-2-[18F]fluoro-D-glucose, to study pathophysiological processes in man non-invasively using positron-emission-tomography (PET) led to a widespread investigation of different 18F-labelled sugars and sugar derivatives. In consideration of the short half-life of fluorine-18 (T(1/2) = 110 min) synthetic strategies concerning precursor design, labelling conditions and deprotection of the intermediate compounds were developed to guarantee an efficient high radiochemical yield synthesis for diagnostic purposes. Besides some aspects of medical application of 2-deoxy-2-[18F]fluoro-D-glucose, a few synthetic strategies are described reflecting development work on promising 18F-labelled sugars for diagnostic purposes during the last two decades.

Expression of the immediate early response gene c-fos is induced by several cellular and extracellular stress factors including ionizing radiation. We examined the role of c-fos in mediating stress-induced apoptosis of isogenic CD4+ and CD8+ mouse T-lymphocytes differing only in their c-fos status after treatment with ionizing radiation and the synthetic glucocorticoid dexamethasone. The amount of radiation-induced apoptosis was decreased (up to 37%) in the T-lymphocyte population derived from the knockout mice lacking endogenous c-fos compared to the wildtype T-lymphocyte population. The difference in apoptosis induction in T-lymphocytes from wildtype and c-fos knockout mice was even more prominent (up to 55%) after dexamethasone treatment. Comparative experiments were performed with T-lymphocytes from isogenic mouse littermates differing only in the status of the tumor-suppressor gene p53. Whereas p53 plays a primary role in radiation-induced apoptosis, our results suggest that c-fos enhances both p53-dependent radiation- and p53-independent steroid-induced apoptosis in T-lymphocytes.

Bacillary angiomatosis is a newly characterized infectious disease occurring mainly in patients with AIDS. Most patients have cutaneous angiomatosis lesions resembling Kaposi's sarcoma or pyogenic granuloma. Although the disease may be life-threatening if not treated, it is curable with appropriate antibiotic therapy. A patient had a fever, nightsweats, abdominal pain, pleural effusions, and asymmetric peripheral lymphadenopathy. Computed tomography of the chest and abdomen revealed a unique pattern of enhancement of lymph nodes that, to this research team's knowledge, has not been reported previously with this condition. Appropriate antibiotic therapy resulted in a complete resolution of the disease. Included is a discussion of the clinical presentation, etiology, histology, and treatment of bacillary angiomatosis.

Fat tissues consist of fat cells, capillaries, and collagen fibers. In order to completely suppress the signals from fat tissues in clinical magnetic resonance imaging, the signal from capillaries and collagen fibers as well as from fat cells should all be suppressed. We have previously reported that fat signal can be uniformly suppressed by applying an optimized presaturation pulse. The inhomogeneously broadened fat peak of tissue spectrum is excited by the optimized pulse and dephased by a subsequent field gradient. The broadened water peak is not affected. In this paper we discuss a technique that suppresses signals from fat tissues completely as well as uniformly. This technique is based on the cancellation of fat and water signals in the same image voxel by combining the optimized selective excitation with the opposite phase imaging technique. Experimental and clinical images demonstrate that the new technique improves the delineation and depiction of anatomy in clinical fat suppression imaging.

Apical membranes of ileal enterocytes contain the major Na+/bile acid cotransporter activity in mammals. Microinjection of guinea pig ileal mucosal Poly A+ mRNA (25 ng) into Xenopus oocytes resulted in 22,23-3H-cholyltaurine uptake at day 3 after injection (453 fmol/oocyte-hr), while control viral mRNA (25 ng) gave an uptake rate of 133 fmol/oocyte-hr. The transport rate increased in direct relationship to the concentration of injected mRNA, cholyltaurine, or Na+ in the incubation media. Uptake of cholyltaurine using rabbit ileal mucosal Poly A+ mRNA was 3891 fmole/oocyte-hr compared to rabbit jejunal-mucosa Poly A+ mRNA (control) injections inducing 728 fmol/oocyte-hr. Such expression of the ileal Na+/bile acid cotransporter may facilitate cloning of this key mammalian gene.

Patients undergoing coronary bypass grafting were studied for incidence of perioperative myocardial infarction (MI) using three modalities: serial electrocardiograms (ECG), serial creatine phosphokinase isoenzymes (MB-CPK), and serial technetium 99m-labeled pyrophosphate scans. A definite perioperative MI was diagnosed if the results were positive in two of the three variables studied. The perioperative infarction rate for the entire group was 8%. The operative mortality was 2.9%. Seven of 8 perioperative MIs were diagnosed by the use of scanning alone. The combination of isoenzyme and ECG analysis diagnosed 5 of 8 perioperative MIs. The MB-CPK and ECG studies were associated with a higher incidence of false-positive diagnoses than myocardial scanning. Patients with perioperative MI had a benign clinical course. Justification for performing three routine 99mTc-pyrophosphate scans on all patients undergoing aortocoronary bypass operation is still to be determined.

The development of acetylcholine (ACh) receptor aggregates at the neuromuscular junction was studied in rat sternomastoid muscles. The first junctional clusters of ACh receptors were loose aggregates of small receptor patches (15 1/2 to 16 1/2 days of gestation). These clusters coalesced to more compact but simple plaques (18 days of gestation to 3 days postnatal). During the first 2 weeks postnatal several changes occurred: the receptor plaque was modified to the adult junctional receptor distribution, multiple innervation was eliminated, and extrajunctional ACh receptors were lost. At the time of birth the receptors in the junctional receptor plaque were already degraded more slowly than were extrajunctional receptors. The junction increased in length most rapidly during the period when the muscle increased most rapidly in mass, from 15 to 100 days postnatal. It is concluded that the junction goes through several stages during development.