I-fibrinogen as an oncophilic radiodiagnostic agent: distribution kinetics in tumour-bearing mice.

Fibrinogen radioiodinated by the iodine monochloride method was tested as a tumour radiodiagnostic agent in mice. The I-fibrinogen cleared from the blood of tumour-bearing mice more rapidly than from that of normal mice, but it cleared from the whole body more slowly, suggesting it accumulated in a substantial tumour-related compartment in the abnormal mice. The tumour concentration steadily increased for 4 h after injection, at which time it reached a peak concentration of 11-4% of the injected dose/g. This concentration was higher than the peak concentration for Ga-citrate (not reached until 24 h) or any other oncophilic radiopharmaceutical tested in this tumour model. The early accumulation is consistent with the use of 123I as a tracer label for fibrinogen. A combination of the large tumour concentration of I-fibrinogen, an increased catabolic rate induced by chemical modification, and the exceptional nuclear properties of 123I for scintigraphic imaging, could lead to a very useful radiodiagnostic procedure for cancer

Vacuum polarization for lukewarm black holes

We compute the renormalized expectation value of the square of a quantum scalar field on a Reissner-Nordström–de Sitter black hole in which the temperatures of the event and cosmological horizons are equal (“lukewarm” black hole). Our numerical calculations for a thermal state at the same temperature as the two horizons indicate that this renormalized expectation value is regular on both the event and cosmological horizons. We are able to show analytically, using an approximation for the field modes near the horizons, that this is indeed the case

Trace Anomaly in Quantum Spacetime Manifold

In this paper we investigate the trace anomaly in a spacetime where single events are de-localized as a consequence of short distance quantum coordinate fluctuations. We obtain a modified form of heat kernel asymptotic expansion which does not suffer from short distance divergences. Calculation of the trace anomaly is performed using an IR regulator in order to circumvent the absence of UV infinities. The explicit form of the trace anomaly is presented and the corresponding 2D Polyakov effective action and energy momentumtensor are obtained. The vacuum expectation value of the energy momentum tensor in the Boulware, Hartle-Hawking and Unruh vacua is explicitly calculated in a (rt)-section of a recently found, noncommutative geometry inspired, Schwarzschild-like solution of the Einstein equations. The standard short distance divergences in the vacuum expectation values are regularized in agreement with the absence of UV infinities removed by quantum coordinate fluctuations.Comment: 15pages, RevTex, no figures, 1 Tabl

Polynomial Time Algorithms for Branching Markov Decision Processes and Probabilistic Min(Max) Polynomial Bellman Equations

We show that one can approximate the least fixed point solution for a multivariate system of monotone probabilistic max(min) polynomial equations, referred to as maxPPSs (and minPPSs, respectively), in time polynomial in both the encoding size of the system of equations and in log(1/epsilon), where epsilon > 0 is the desired additive error bound of the solution. (The model of computation is the standard Turing machine model.) We establish this result using a generalization of Newton's method which applies to maxPPSs and minPPSs, even though the underlying functions are only piecewise-differentiable. This generalizes our recent work which provided a P-time algorithm for purely probabilistic PPSs. These equations form the Bellman optimality equations for several important classes of infinite-state Markov Decision Processes (MDPs). Thus, as a corollary, we obtain the first polynomial time algorithms for computing to within arbitrary desired precision the optimal value vector for several classes of infinite-state MDPs which arise as extensions of classic, and heavily studied, purely stochastic processes. These include both the problem of maximizing and mininizing the termination (extinction) probability of multi-type branching MDPs, stochastic context-free MDPs, and 1-exit Recursive MDPs. Furthermore, we also show that we can compute in P-time an epsilon-optimal policy for both maximizing and minimizing branching, context-free, and 1-exit-Recursive MDPs, for any given desired epsilon > 0. This is despite the fact that actually computing optimal strategies is Sqrt-Sum-hard and PosSLP-hard in this setting. We also derive, as an easy consequence of these results, an FNP upper bound on the complexity of computing the value (within arbitrary desired precision) of branching simple stochastic games (BSSGs)

The Fulling-Unruh effect in general stationary accelerated frames

We study the generalized Unruh effect for accelerated reference frames that include rotation in addition to acceleration. We focus particularly on the case where the motion is planar, with presence of a static limit in addition to the event horizon. Possible definitions of an accelerated vacuum state are examined and the interpretation of the Minkowski vacuum state as a thermodynamic state is discussed. Such athermodynamic state is shown to depend on two parameters, the acceleration temperature and a drift velocity, which are determined by the acceleration and angular velocity of the accelerated frame. We relate the properties of Minkowski vacuum in the accelerated frame to the excitation spectrum of a detector that is stationary in this frame. The detector can be excited both by absorbing positive energy quanta in the "hot" vacuum state and by emitting negative energy quanta into the "ergosphere" between the horizon and the static limit. The effects are related to similar effects in the gravitational field of a rotating black hole.Comment: Latex, 39 pages, 5 figure

Black Hole Evaporation in an Expanding Universe

We calculate the quantum radiation power of black holes which are asymptotic to the Einstein-de Sitter universe at spatial and null infinities. We consider two limiting mass accretion scenarios, no accretion and significant accretion. We find that the radiation power strongly depends on not only the asymptotic condition but also the mass accretion scenario. For the no accretion case, we consider the Einstein-Straus solution, where a black hole of constant mass resides in the dust Friedmann universe. We find negative cosmological correction besides the expected redshift factor. This is given in terms of the cubic root of ratio in size of the black hole to the cosmological horizon, so that it is currently of order $10^{-5} (M/10^{6}M_{\odot})^{1/3} (t/14 {Gyr})^{-1/3}$ but could have been significant at the formation epoch of primordial black holes. Due to the cosmological effects, this black hole has not settled down to an equilibrium state. This cosmological correction may be interpreted in an analogy with the radiation from a moving mirror in a flat spacetime. For the significant accretion case, we consider the Sultana-Dyer solution, where a black hole tends to increase its mass in proportion to the cosmological scale factor. In this model, we find that the radiation power is apparently the same as the Hawking radiation from the Schwarzschild black hole of which mass is that of the growing mass at each moment. Hence, the energy loss rate decreases and tends to vanish as time proceeds. Consequently, the energy loss due to evaporation is insignificant compared to huge mass accretion onto the black hole. Based on this model, we propose a definition of quasi-equilibrium temperature for general conformal stationary black holes.Comment: Accepted for publication in Class.Quant.Grav., 18 pages and 3 figure

SPLENIC VOLUME CHANGE AND THERAPUETIC RESPONSE IN PATIENTS TREATED WITH RADIOMMUNOCONJUGATES

Splenomegaly is frequently found in non-Hodgkin's lymphoma (NHL) patients. This study evaluated the implications of splenic volume change in response to radioimmunotherapy (RIT). Twenty-nine NHL patients treated with radiolabeled-Lym-1 and 9 breast cancer patients (reference group) treated with radiolabeled-ChL6, BrE-3 or m170 were analyzed using CT splenic images obtained before and after RIT. Patient-specific radiation doses to spleen were determined using actual splenic volume determined by CT and body weight. In 13 of 29 NHL patients who had splenic volume {le} 310 ml, there was no or small change (-23 to 15 mL) in splenic volume, despite splenic doses as high as 14.4 Gy. Similarly, in a reference group of 9 breast cancer patients, there was no or small change (-5 to 13 mL), despite splenic doses as high as 11.4 Gy. In contrast, 13 of 29 NHL patients who had splenic volume 380-1400 mL, splenic volume decreased by 68 to 548 mL despite splenic doses as low as 1.40 Gy. Ten of 29 NHL patients with greater than a 15% decrease in splenic volume after RIT had nodal tumor regression (5 CR, 5 PR). In the remaining 19 NHL patients with less than a 15% decrease in splenic volume after RIT, there were 7 non-responders (5 CR and 7 PR). Splenic volume changes were found in NHL patients with splenomegaly. These splenic volume changes is likely due to therapeutic effect on malignant lymphocytes associated with splenomegaly. Nodal tumor response was more likely when splenomegaly decreased after RIT

Kinks Dynamics in One-Dimensional Coupled Map Lattices

We examine the problem of the dynamics of interfaces in a one-dimensional space-time discrete dynamical system. Two different regimes are studied : the non-propagating and the propagating one. In the first case, after proving the existence of such solutions, we show how they can be described using Taylor expansions. The second situation deals with the assumption of a travelling wave to follow the kink propagation. Then a comparison with the corresponding continuous model is proposed. We find that these methods are useful in simple dynamical situations but their application to complex dynamical behaviour is not yet understood.Comment: 17pages, LaTex,3 fig available on cpt.univ-mrs.fr directory pub/preprints/94/dynamical-systems/94-P.307

In-Vivo Biodistribution and Safety of 99mTc-LLP2A-HYNIC in Canine Non-Hodgkin Lymphoma

Theranostic agents are critical for improving the diagnosis and treatment of non-Hodgkin Lymphoma (NHL). The peptidomimetic LLP2A is a novel peptide receptor radiotherapy candidate for treating NHL that expresses the activated α4β1 integrin. Tumor-bearing dogs are an excellent model of human NHL with similar clinical characteristics, behavior, and compressed clinical course. Canine in vivo imaging studies will provide valuable biodistribution and affinity information that reflects a diverse clinical population of lymphoma. This may also help to determine potential dose-limiting radiotoxicity to organs in human clinical trials. To validate this construct in a naturally occurring model of NHL, we performed in-vivo molecular targeted imaging and biodistribution in 3 normal dogs and 5 NHL bearing dogs. 99mTc-LLP2A-HYNIC-PEG and 99mTc-LLP2A-HYNIC were successfully synthesized and had very good labeling efficiency and radiochemical purity. 99mTc-LLP2A-HYNIC and 99mTc-LLP2A-HYNIC-PEG had biodistribution in keeping with their molecular size, with 99mTc-LLP2A-HYNIC-PEG remaining longer in the circulation, having higher tissue uptake, and having more activity in the liver compared to 99mTc-LLP2A-HYNIC. 99mTc-LLP2A-HYNIC was mainly eliminated through the kidneys with some residual activity. Radioactivity was reduced to near-background levels at 6 hours after injection. In NHL dogs, tumor showed moderately increased activity over background, with tumor activity in B-cell lymphoma dogs decreasing after chemotherapy. This compound is promising in the development of targeted drug-delivery radiopharmaceuticals and may contribute to translational work in people affected by non-Hodgkin lymphoma