Optimal Timing for Assessment of Tumor Response to Neoadjuvant Chemoradiation in Patients With Rectal Cancer: Do All Patients Benefit From Waiting Longer Than 6 Weeks?

Purpose: To estimate the metabolic activity of rectal cancers at 6 and 12 weeks after completion of chemoradiation therapy (CRT) by 2-[fluorine-18] fluoro-2-deoxy-D-glucose-labeled positron emission tomography/computed tomography ([18 FDG] PET/CT) imaging and correlate with response to CRT. Methods and Materials: Patients with cT2-4N0-2M0 distal rectal adenocarcinoma treated with long-course neoadjuvant CRT (54 Gy, 5-fluouracil-based) were prospectively studied (ClinicalTrials. org identifier NCT00254683). All patients underwent 3 PET/CT studies (at baseline and 6 and 12 weeks fromCRT completion). Clinical assessment was at 12 weeks. Maximal standard uptakevalue (SUVmax) of the primary tumor wasmeasured and recorded at eachPET/CTstudy after 1 h (early) and3 h (late) from 18 FDGinjection. Patientswith an increase in early SUVmax between 6 and 12 weeks were considered " bad" responders and the others as "good" responders. Results: Ninety-one patients were included; 46 patients (51%) were "bad" responders, whereas 45 (49%) patients were " good" responders. " Bad" responders were less likely to develop complete clinical response (6.5% vs. 37.8%, respectively; PZ. 001), less likely to develop significant histological tumor regression (complete or near-complete pathological response; 16% vs. 45%, respectively; PZ. 008) and exhibited greater final tumor dimension (4.3cmvs. 3.3cm; PZ. 03). Decrease between early (1 h) and late (3 h) SUVmax at 6-week PET/CTwas a significant predictor of " good" response (accuracy of 67%). Conclusions: Patients who developed an increase in SUVmax after 6 weeks were less likely to develop significant tumor downstaging. Early-late SUVmax variation at 6-week PET/CT may help identify these patients and allow tailored selection of CRT-surgery intervals for individual patients. (C) 2012 Elsevier Inc.

Cortical activation during executed, imagined, observed, and passive wrist movements in healthy volunteers and stroke patients

Motor imagery, passive movement, and movement observation have been suggested to activate the sensorimotor system without overt movement. The present study investigated these three covert movement modes together with overt movement in a within-subject design to allow for a fine-grained comparison of their abilities in activating the sensorimotor system, i.e. premotor, primary motor, and somatosensory cortices. For this, 21 healthy volunteers underwent functional magnetic resonance imaging (fMRI). In addition we explored the abilities of the different covert movement modes in activating the sensorimotor system in a pilot study of 5 stroke patients suffering from chronic severe hemiparesis. Results demonstrated that while all covert movement modes activated sensorimotor areas, there were profound differences between modes and between healthy volunteers and patients. In healthy volunteers, the pattern of neural activation in overt execution was best resembled by passive movement, followed by motor imagery, and lastly by movement observation. In patients, attempted overt execution was best resembled by motor imagery, followed by passive movement and lastly by movement observation. Our results indicate that for severely hemiparetic stroke patients motor imagery may be the preferred way to activate the sensorimotor system without overt behavior. In addition, the clear differences between the covert movement modes point to the need for within-subject comparisons. (C) 2012 Elsevier Inc. All rights reserved.

Exact correlation functions in particle-reaction models with immobile particles

Exact results on particle densities as well as correlators in two models of immobile particles, containing either a single species or else two distinct species, are derived. The models evolve following a descent dynamics through pair annihilation where each particle interacts once at most throughout its entire history. The resulting large number of stationary states leads to a non-vanishing configurational entropy. Our results are established for arbitrary initial conditions and are derived via a generating function method. The single-species model is the dual of the 1D zero-temperature kinetic Ising model with Kimball-Deker-Haake dynamics. In this way, both in finite and semi-infinite chains and also the Bethe lattice can be analysed. The relationship with the random sequential adsorption of dimers and weakly tapped granular materials is discussed.

New molecular targets for PET and SPECT imaging in neurodegenerative diseases

The pathophysiology of neurodegenerative diseases (ND) such as Alzheimer's disease (AD) and Parkinson's disease (PD) has not yet been completely elucidated. However, in the past few years, there have been great knowledge advances about intra-and extracellular proteins that may display impaired function or expression in AD, PD and other ND, such as amyloid beta (AB), alpha-synuclein, tau protein and neuroinfiammatory markers. Recent developments in the imaging techniques of positron emission tomography (PET) and single photon emission computed tomography (SPECT) now allow the non-invasive tracking of such molecular targets of known relevance to ND in vivo. This article summarizes recent findings of PET and SPECT studies using these novel methods, and discusses their potential role in the field of drug development for ND as well as future clinical applications in regard to differential diagnosis of ND and monitoring of disease progression.

Production of K*(892)(0) and phi(1020) in pp collisions at root s=7 TeV

The production of K*(892)(0) and phi(1020) in pp collisions at root s = 7 TeV was measured by the ALICE experiment at the LHC. The yields and the transverse momentum spectra d(2)N/dydp(T) at midrapidity vertical bar y vertical bar < 0.5 in the range 0 < p(T) < 6 GeV/c for K*(892)(0) and 0.4 < p(T) < 6 GeV/c for phi(1020) are reported and compared to model predictions. Using the yield of pions, kaons, and Omega baryons measured previously by ALICE at root s = 7 TeV, the ratios K*/K-, phi/K*, phi/ K-, phi/pi(-), and (Omega + <(Omega)over bar>)/phi are presented. The values of the K*/K-, phi/K* and phi/K- ratios are similar to those found at lower centre-of-mass energies. In contrast, the phi/pi(-) ratio, which has been observed to increase with energy, seems to saturate above 200 GeV. The (Omega + (Omega) over bar)/phi ratio in the p(T) range 1-5 GeV/ c is found to be in good agreement with the prediction of the HIJING/B (B) over bar v2.0model with a strong colour field.

Pathophysiology of mood disorders in temporal lobe epilepsy

Objective: There is accumulating evidence that the limbic system is pathologically involved in cases of psychiatric comorbidities in temporal lobe epilepsy (TLE) patients. Our objective was to develop a conceptual framework describing how neuropathological, neurochemical and electrophysiological aspects might contribute to the development of psychiatric symptoms in TLE and the putative neurobiological mechanisms that cause mood disorders in this patient subgroup. Methods: In this review, clinical, experimental and neuropathological findings, as well as neurochemical features of the limbic system were examined together to enhance our understanding of the association between TLE and psychiatric comorbidities. Finally, the value of animal models in epilepsy and mood disorders was discussed. Conclusions: TLE and psychiatric symptoms coexist more frequently than chance would predict. Alterations and neurotransmission disturbance among critical anatomical networks, and impaired or aberrant plastic changes might predispose patients with TLE to mood disorders. Clinical and experimental studies of the effects of seizures on behavior and electrophysiological patterns may offer a model of how limbic seizures increase the vulnerability of TLE patients to precipitants of psychiatric symptoms.

CP asymmetries in the supersymmetric trilepton signal at the LHC

In the CP-violating Minimal Supersymmetric Standard Model, we study the production of a neutralino-chargino pair at the LHC. For their decays into three leptons, we analyze CP asymmetries which are sensitive to the CP phases of the neutralino and chargino sector. We present analytical formulas for the entire production and decay process, and identify the CP-violating contributions in the spin correlation terms. This allows us to define the optimal CP asymmetries. We present a detailed numerical analysis of the cross sections, branching ratios, and the CP observables. For light neutralinos, charginos, and squarks, the asymmetries can reach several 10%. We estimate the discovery potential for the LHC to observe CP violation in the trilepton channel.

A tomografia por emissão de pósitrons com 2-[18F]-fluoro-2-desoxi-D-glicose é custo-efetiva em pacientes com câncer de pulmão não pequenas células no Brasil

OBJETIVO: Comparar a acurácia e a custo-efetividade do estadiamento metabólico (EM) com o FDG-PET em relação ao estadiamento convencional (EC) no estadiamento inicial de pacientes com câncer de pulmão não pequenas células (CPNPC). MATERIAIS E MÉTODOS: Noventa e cinco pacientes com diagnóstico inicial de CPNPC foram estadiados antes do início do tratamento. Os resultados do EC e EM foram comparados quanto a definição do tratamento e incidência de toracotomia fútil em cada estratégia. RESULTADOS: O EM com FDG-PET classificou 48,4% dos pacientes como estádio mais avançado e 5,3% como menos avançado. O resultado do EM modificaria o tratamento em 41% dos pacientes. A toracotomia foi considerada fútil em 47% dos pacientes com EC e em 19% dos casos com EM. O custo das toracotomias fúteis em oito pacientes no EM foi de R$ 79.720, enquanto em 31 pacientes no EC seria de R$ 308.915. Apenas esta economia seria mais que suficiente para cobrir os custos de todos os exames de FDG-PET nos 95 pacientes (R$ 126.350) ou de FDG-PET/CT (R$ 193.515). CONCLUSÃO: O EM com FDG-PET tem maior acurácia que o EC em pacientes com CPNPC. A FDG-PET e FDG-PET/CT são custo-efetivas e sua utilização se justifica economicamente na saúde pública no Brasil.

Non-neoplastic bulky mediastinal mass presentation in an adolescent patient: a case report

Abstract : Introduction Mediastinal masses in pediatric patients are very heterogeneous in origin and etiology. In the first decade of life, 70% of the mediastinal masses are benign whereas malignant tumors are more frequent in the second decade of life. Among the mediastinal masses, lymph nodes are the most common involved structures and could be enlarged due to a lymphoma, leukemia, metastatic disease, or due to infectious diseases as sarcoidosis, tuberculosis and others. Case presentation. We report a case of a 13-year-old Caucasian girl who came to the emergency room with a history of intermittent fever, weight loss and night sweating for at least 1 month. A radiologic image work-up presented an anterior and posterior mediastinal mass. The 18F-fluorodeoxyglucose positron emission tomography presented a high maximum standard uptake value, which directed our decision for mediastinal biopsy for diagnostic elucidation. Histologic examination described the mass as granulomatous tuberculosis. The patient was treated with anti-tuberculosis therapy and developed a full clinical recovery. Conclusions . The present case report demonstrates that a bulky mediastinal lymphadenopathy detected on 18F-fluorodeoxyglucose positron emission tomography is not always a malignant lesion, and in countries where tuberculosis is endemic, this etiology should not be forgotten during clinical investigations. There is a need for more accurate cut-off values for this technology; meanwhile, the further investigation of patients with bulky mediastinal masses with procedures such as the open biopsy is indispensable.

Serch for Neutralino Dark Matter with the AMANDA-II Neutrino Telescope

The annihilation of weakly interacting massive particles (WIMPs), accumulated in gravitational potentials (e.g., the core of the Earth, the Sun or the Galactic halo) would lead to neutrino production. This thesis investigates the possibility of searching for WIMPs in the form of the lightest supersymmetric particle (neutralino) trapped in the Sun using the AMANDA-II neutrino telescope. AMANDA-II is a large Cherenkov detector located deep in the ice at the geographical South Pole. The presented work is based on data taken during the year 2001. An analysis optimized to search for the neutralino-induced flux from the Sun has been developed. The observation of no excess with respect to the expected atmospheric neutrino background has been interpreted as an upper limit on the neutralino annihilation rate in the Sun and on the neutralino-induced muon flux in the vicinity of the detector.

A Dark Matter Search with AMANDA : Limits on the Muon Flux from Neutralino Annihilations at the Centre of the Earth with 1997-99 Data

The nature of the dark matter in the Universe is one of the greatest mysteries in modern astronomy. The neutralino is a nonbaryonic dark matter candidate in minimal supersymmetric extensions to the standard model of particle physics. If the dark matter halo of our galaxy is made up of neutralinos some would become gravitationally trapped inside massive bodies like the Earth. Their pair-wise annihilation produces neutrinos that can be detected by neutrino experiments looking in the direction of the centre of the Earth. The AMANDA neutrino telescope, currently the largest in the world, consists of an array of light detectors buried deep in the Antarctic glacier at the geographical South Pole. The extremely transparent ice acts as a Cherenkov medium for muons passing the array and using the timing information of detected photons it is possible to reconstruct the muon direction. A search has been performed for nearly vertically upgoing neutrino induced muons with AMANDA-B10 data taken over the three year period 1997-99. No excess above the atmospheric neutrino background expectation was found. Upper limits at the 90 % confidence level has been set on the annihilation rate of neutralinos at the centre of the Earth and on the muon flux induced by neutrinos created by the annihilation products.

Strahlungskorrekturen zu Polarisationsobservablen schwerer Quarks

Das Thema der Dissertation ist die analytische Berechnung von QCD-Strahlungskorrekturen erster Ordnung zurPolarisation schwerer und leichter Quarks in der $e^+ e^-$-Vernichtung,und der Polarisation von Gluonen, die bei der Produktion von leichten oderschweren Quarkpaaren in der $e^+ e^-$-Vernichtung abgestrahlt werden. Der erste Teil der Arbeit (Kapitel 1 und 2) befaßt sich mitder vollständigen Analyse der Gluonpolarisation für den Prozeß $e^+ e^- to q bar q G$ und $ Q bar Q G$. Es werdenBerechnungen derQCD-Bremsstrahlungskorrekturen zur ersten Ordnung in$alpha_s$ zur Gluonpolarisation im Prozeß $e^+ e^- to q bar q G$ und$ Q bar Q G$ durchgeführt. Ferner werden die lineare und die zirkulareGluonpolarisation in der Hadronebene und Leptonebene untersucht. Anschließend werden die Polarwinkelabhängigkeit und dieStrahlpolarisationsabhängigkeit der Gluonpolarisation analysiert. Im zweiten Teil der Arbeit (Kapitel 3 und 4) finden sich die Berechnungen der QCD-Strahlungskorrekturen erster Ordnungfür massive Quarkszur Longitudinal-Longitudinal Spin-Korrelation für dieProzeße $e^+ e^- to q bar q$ und $Q bar Q$. In Kapitel 3 wirdeine Mittelung überdie Polarwinkel durchgeführt, während in Kapitel 4 die Polarwinkel-Abhängigkeit explizit untersucht wird. ImKapitel 3 und 4 wird der Effekt der $O(alpha_s)$-Korrektur zur spin-flip-Konfiguration der verschiedenen Komponenten derHadrontensoren diskutiert. Der vorgelegten Arbeit kommt im Rahmen der für die Zukunftgeplanten Hochpräzisionsexperimente eine besondere Bedeutung zu, dasie Vorhersagen für Spinobservablen liefert, die in Experimentenan den geplanten $e^+ e^-$-Linearbeschleunigern gemessen werden können.

Synthese, n.c.a. 18F-Markierung und Evaluierung von Antagonisten der Strychnin-unempfindlichen-Glycinbindungsstelle auf Basis der 4-Amino-5,7-Dichlor-1,2,3,4-Tetrahydro-Chinolin-2-Carbonsäure

ZUSAMMENFASSUNGDer glutamaterge N-Methyl-D-aspartat-Rezeptor (NMDA) ist ein wichtiger ionotroper Rezeptor, der die exzitatorische synaptische Transmission im zentralen Nervensystem von Säugetieren vermittelt. Der NMDA-Rezeptor nimmt unter den Glutamatrezeptoren dabei eine Sonderstellung ein, da er mit einer Reihe von neurodegenerativen Erkrankungen wie dem Morbus Parkinson, dem Morbus Huntington, dem Morbus Alzheimer, der Schizophrenie und der Epilepsie in Zusammenhang gebracht wird. Daher besteht ein großes Interesse an der Entwicklung geeigneter 18F-markierter NMDA-Rezeptorliganden zur nicht-invasiven Visualisierung des NMDA-Rezeptorkomplexes mittels der Positronenemissionstomographie.Die 19F-Analoga ADTC1, tADTC1 und tADTC3 - 5 und das nicht-fluorierte 12C-Analogon tADTC2 wurden synthetisiert und ihre in-vitro Affinität und Lipophilie bestimmt. Mit Ausnahme von ADTC1 und tADTC5 die mikromolare Affinitäten besitzen, haben die Liganden in [H-3]MDL-105,519 Rezeptorbindungsassays niedrige nanomolare Affinitäten für die Glycinbindungsstelle. Die Lipophilie der Verbindungen wurde mit drei verschiedenen Verfahren untersucht und ergab logD7,4-Werte von ungefähr 1 für cADTC1 und tADTC1 – 4, während tADTC5 mit einem logD7,4 von –1,15 eine sehr niedrige Lipophilie aufwies. Die Radiosynthesen der 18F-Liganden wurden hinsichtlich der Umsetzung der Markierungsvorläufer mit 2-[F-18]Fluorethyltosylat oder [F-18]Fluorid untersucht und optimiert. Die höchsten radiochemischen Ausbeuten von ungefähr 90% wurden, unter Verwendung von NaOH als Hilfsbase, bei der 18F-Fluorethylierung von t[F-18]ADTC4 und t[F-18]ADTC5 mit 2-[F-18]Fluorethyltosylat erzielt.

Synthese, 11 C- und 18 F-Markierung und Evaluierung von Repaglinid-Derivaten zur Quantifizierung der pankreatischen beta-Zell-Masse in vivo mittels PET

Diabetes mellitus umfasst eine heterogene Gruppe von Stoffwechselfunktionsstörungen, die durch hohe Blut-Glukose-Werte gekennzeichnet sind. Zwei Haupttypen von Diabetes mellitus wurden definiert: Typ 1- und Typ 2-Diabetes. Repaglinid ist ein neuer, schnell wirksamer, bei Typ 2-Diabetikern eingesetzter prandialer Glukose-Regulator mit einer kurzen Plasmahalbwertszeit (<1 Stunde) und der erste Vertreter der Carbamoylmethylbenzoesäure Familie, der in klinischen Studien getestet wurde. Die 18F- und 11C-markierten Repaglinid-Derivate (S)-2-(2-[18F]Fluorethoxy)-4-((3-methyl-1-(2-piperidin-1-yl-phenyl)-butylcarbamoyl)-methyl)-benzoesäure ([18F]Fluorethoxy-desethoxy-Repaglinid) und (S)-2-([11C]Methoxy)-4-([3-methyl-1-(2-piperidin-1-yl-phenyl)-butyl-carba-moyl]-benzoesäure ([11C]Methoxy-desethoxy-Repaglinid) wurden als potentielle Tracer für die nicht-invasive Quantifizierung des Sulfonylharnstoffrezeptor-Typ1-Status (SUR-1) der Insulin-sezernierenden -Zellen mittels Positronen-Emissions-Tomographie (PET) synthetisiert. [18F]Fluorethoxy-desethoxy-Repaglinide konnte in einer radiochemischen Ausbeute (RCA) von 20% nach 135 Minuten mit einer radiochemischen Reinheit >98% unter Verwendung des sekundären Markierungsvorläufers 2-[18F]Fluorethyltosylat erhalten werden. Die spezifische Aktivität lag im Bereich von 50-60 GBq/µmol. Für die radioaktive Synthese des [11C]Methoxy-desethoxy-Repaglinids wurde der sekundäre Markierungsvorläufer [11C]Methyliodid verwendet. Der 11C-Radiotracer wurde in einer RCA von 35% (bezogen auf [11C]CO2) mit einer spezifischen Aktivität von 40-70 GBq/µmol erhalten. Um die Eigenschaften des fluorierten sowie des methoxylierten Repaglinids zu charakterisieren, wurde die Affinität beider Verbindungen zum humanen SUR-1 evaluiert. [19F]Fluorethoxy-desethoxy-Repaglinid und Methoxy-desethoxy-Repaglinid induzierten Verdrängungskurven mit Hill-Koeffizienten nahe 1 und ergaben Dissotiationskonstanten (KD) von 142 nM beziehungsweise 83 nM - vergleichsweise geringe Verluste relativ zu Original-Repaglinid. Die biologische Aktivität wurde mittels Insulin-Sekretionstests an isolierten Ratten-Inselzellen gezeigt und war ebenfalls mit der des Repaglinids vergleichbar. Schließlich wurde die Biodistribution des [18F]Fluorethoxy-desethoxy-Repaglinids in gesunden Sprague-Dawley-Ratten durch Messung der Konzentration der Verbindung in verschiedenen Organen nach intravenöser Injektion untersucht. Das pankreatische Gewebe zeigte im Zeitintervall zwischen 10 und 30 Minuten nach Injektion eine stabile Akkumulation von etwa 0.12% der injizierten Dosis. 50% dieser Tracer-Akkulmulation konnten durch zusätzliche Injektion von nicht-radioaktiv-markiertem Repaglinid verdrängt werden, was auf eine mögliche Eignung des [18F]Fluorethoxy-desethoxy-Repaglinids für in vivo-Untersuchungen mittels PET schließen lässt. Eine erste humane PET-Studie zeigte zwar ebenfalls eine stabile, allerdings nur geringere Akkumulation von [18F]Fluorethoxy-desethoxy-Repaglinid im Pankreas und eine überproportional hohe Aktivitätsanreicherung in der Leber. Die Radioaktivitäts-akkumulation im Blut fiel nach wenigen Minuten unter die des Pankreas.

Production, radiochemical separation and chemical coupling of radioactive arsenic isotopes to synthesize radiopharmaceuticals for molecular imaging

Noninvasive molecular-imaging technologies are playing a keyrole in drug discovery, development and delivery. Positron Emission Tomography (PET) is such a molecular imaging technology and a powerful tool for the observation of various diseases. However, it is limited by the availability of agents with high selectivity to the target and a physical half-life of the used positron emitting nuclide which matches the biological half-life of the observed process. For the long lasting enrichment of antibodies in tumor tissue few suitable isotopes for PET imaging are currently available. The element arsenic provides a range of isotopes, which could be used for diagnosis and also for endoradiotherapy. This work describes the development of radiochemical separation procedures to separate arsenic isotopes in no-carrier-added (nca) purity from reactor or cyclotron irradiated targets, the development and evaluation of a labeling chemistry to attach these separated arsenic isotopes to monoclonal antibodies, the in vitro and in vivo evaluation of antibodies labeled with radioactive arsenic isotopes and the molecular imaging using small animal PET.