Optimal Entanglement Swapping in Quantum Repeaters.

We formulate the problem of finding the optimal entanglement swapping scheme in a quantum repeater chain as a Markov decision process and present its solution for different repeaters' sizes. Based on this, we are able to demonstrate that the commonly used "doubling" scheme for performing probabilistic entanglement swapping of probabilistically distributed entangled qubit pairs in quantum repeaters does not always produce the best possible raw rate. Focusing on this figure of merit, without considering additional probabilistic elements for error suppression such as entanglement distillation on higher "nesting levels," our approach reveals that a power-of-two number of segments has no privileged position in quantum repeater theory; the best scheme can be constructed for any number of segments. Moreover, classical communication can be included into our scheme, and we show how this influences the raw waiting time for different numbers of segments, confirming again the optimality of "nondoubling" in some relevant parameter regimes. Thus, our approach provides the minimal possible waiting time of quantum repeaters in a fairly general physical setting.

Investigation of the metabolites of (S,S)-[(11)C]MeNER in humans, monkeys and rats.

INTRODUCTION: (S,S)-[(11)C]MeNER ((S,S)-2-(alpha-(2-[(11)C]methoxyphenoxy)benzyl)morpholine) is a positron emission tomography (PET) radioligand recently applied in clinical studies of norepinephrine transporters (NETs) in the human brain in vivo. In view of further assessment of the suitability of (S,S)-[(11)C]MeNER as a NET radioligand, its metabolism and the identity of the in vivo radiometabolites of (S,S)-[(11)C]MeNER are of great interest. MATERIALS AND METHODS: Thus, PET studies were used to measure brain dynamics of (S,S)-[(11)C]MeNER, and plasma reverse-phase radiochromatographic analysis was performed to monitor and quantify its rate of metabolism. Eighteen healthy human volunteers, five cynomolgus monkeys, and five rats were studied. RESULTS AND DISCUSSION: In human subjects, the plasma radioactivity representing (S,S)-[(11)C]MeNER decreased from 88 +/- 5% at 4 min after injection to 82 +/- 7% at 40 min, while a polar radiometabolite increased from 3 +/- 3% to 16 +/- 7% at the same time-points, respectively. A more lipophilic radiometabolite than (S,S)-[(11)C]MeNER decreased from 9 +/- 5% at 4 min to 1 +/- 2% at 40 min. In monkeys, plasma radioactivity representing (S,S)-[(11)C]MeNER decreased from 97 +/- 2% at 4 min to 74 +/- 7% at 45 min, with a polar fraction as the major radiometabolite. A more lipophilic radiometabolite than (S,S)-[(11)C]MeNER, constituted 3 +/- 2% of radioactivity at 4 min and was not detectable later on. In rats, 17 +/- 4% of plasma radioactivity was parent radioligand at 30 min with the remainder comprising mainly a polar radiometabolite. (S,S)-[(11)C]MeNER in rat brain and urine at 30 min after injection were 90% and 4%, respectively. On a brain regional level, parent radioligand ranged from 87.5 +/- 3.9% (57.2 +/- 14.2% SUV [standard uptake values, %injected radioactivity per mL multiplied with animal weight (in g)]; cerebellum) to 92.9 +/- 1.8% (36.1 +/- 4.7% SUV; striatum), with differential distribution of the radiometabolite in the cerebellum (6.7 +/- 0.3% SUV) and the striatum (2.5 +/- 0.3% SUV). Liquid chromatography-mass spectrometry analysis of rat urine identified a hydroxylation product of the methoxyphenoxy ring of (S,S)-MeNER as the main metabolite. In the brain, the corresponding main metabolite was the product from O-de-methylation of (S,S)-MeNER. PET measurements were performed in rats as well as in wild-type and P-gp-knock-out mice. In rats, the brain peak level of radioactivity was found to be very low (65%SUV). In mice, there was only a small difference in peak brain accumulation between P-gp knock-out and wild-type mice (145 vs. 125%SUV) with the following rank order of regional brain radioactivity: cerebellum x thalamus > cortical regions > striatum. CONCLUSION: It can be concluded that radiometabolites of (S,S)-[(11)C]MeNER are of minor importance in rat and monkey brain imaging. The presence of a transient lipophilic radiometabolite in peripheral human plasma may induce complications with brain imaging, but its kinetics appear favorable in relation to the slow kinetics of (S,S)-[(11)C]MeNER in humans.

[11C]vinpocetine: a prospective peripheral benzodiazepine receptor ligand for primate PET studies.

Vinpocetine, a synthetic derivative of the Vinca minor alkaloid vincamine, is a widely used drug in neurological practice. We tested the hypothesis that vinpocetine binds to peripheral benzodiazepine binding sites (PBBS) and is therefore a potential ligand of PBBS. Positron emission tomography (PET) measurements in two cynomolgous monkeys showed that pretreatment with vinpocetine markedly reduced the brain uptake of [11C]PK11195, a known PBBS radioligand. On the other hand, whereas pretreatment with PK11195 increased the brain uptake of [11C]vinpocetine due to the blockade of PBBS in the periphery, it significantly reduced the binding potential (BP) values of [11C]vinpocetine in the whole brain and in individual brain structures to PK11195. These findings indicate that, whereas the two ligands have different affinities to PBBS, vinpocetine is a potent ligand of PBBS, which in turn suggests that the pharmacological activity of vinpocetine may involve the regulation of glial functions.

A preliminary PET evaluation of the new dopamine D2 receptor agonist [11C]MNPA in cynomolgus monkey.

This study describes the preliminary positron emission tomography (PET) evaluation of a dopamine D(2)-like receptor agonist, (R)-2-(11)CH(3)O-N-n-propylnorapomorphine ([(11)C]MNPA), as a potential new radioligand for in vivo imaging of the high-affinity state of the dopamine D(2) receptor (D(2)R). MNPA is a selective D(2)-like receptor agonist with a high affinity (K(i)=0.17 nM). [(11)C]MNPA was successfully synthesized by direct O-methylation of (R)-2-hydroxy-NPA using [(11)C]methyl iodide and was evaluated in cynomolgus monkeys. This study included baseline PET experiments and a pretreatment study using unlabeled raclopride (1 mg/kg). High uptake of radioactivity was seen in regions known to contain high D(2)R, with a maximum striatum-to-cerebellum ratio of 2.23+/-0.21 at 78 min and a maximum thalamus-to-cerebellum ratio of 1.37+/-0.06 at 72 min. The pretreatment study demonstrated high specific binding to D(2)R by reducing the striatum-to-cerebellum ratio to 1.26 at 78 min. This preliminary study indicates that the dopamine agonist [(11)C]MNPA has potential as an agonist radioligand for the D(2)-like receptor and has potential for examination of the high-affinity state of the D(2)R in human subjects and patients with neuropsychiatric disorders.

Preparation of highly specific radioactivity [18F]flumazenil and its evaluation in cynomolgus monkey by positron emission tomography.

A straightforward method for the preparation of no-carrier-added (n.c.a.) [18F]flumazenil via standard nucleophilic radiofluorination of the corresponding nitro-analog Ro 15-2344 has been developed. The labeling was performed by employing the K18F/kryptofix complex in DMF at 160 degrees C for 30 min and equimolar ratio [K/K2.2.2]+18F-/precursor. Under these conditions, an 18F incorporation rate into flumazenil was in the range of 55-60%. The final product was isolated by HPLC purification within a total synthesis time of 75 min and a radiochemical yield of about 30% (EOB). Human post-mortem whole-hemisphere autoradiography of brain sections demonstrated selective uptake of the radioligand in the areas of high density of the central benzodiazepine receptors (BZR). PET studies in a cynomolgus monkey and metabolite studies by HPLC demonstrated similar results by [18F]flumazenil as for [11C]flumazenil. In blocking experiments, almost all radioactivity was inhibited by the addition of unlabeled flumazenil. [18F]Flumazenil is a suitable radioligand for PET assessment of the BZR.

A fully automated one-pot synthesis of [carbonyl-11C]WAY-100635 for clinical PET applications.

A fully automated synthesis of the important 5HT(1A) receptor radioligand, [carbonyl-(11)C]WAY-100635 (I), was developed based on the optimized one-pot "wet" synthesis procedure. A modern automated apparatus was constructed from commercially available components and operated via LabView software. In average, (906+/-525)MBq (n=94) of (I) was obtained from 40 min bombardment at 50 microA beam current within 50 min synthesis time. The specific radioactivity (SA) at the time of injection was (50.5+/-29.3)GBq/mumol (n=94).