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

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

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

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

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

One-Loop Renormalization of a Self-Interacting Scalar Field in Nonsimply Connected Spacetimes

Using the effective potential, we study the one-loop renormalization of a massive self-interacting scalar field at finite temperature in flat manifolds with one or more compactified spatial dimensions. We prove that, owing to the compactification and finite temperature, the renormalized physical parameters of the theory (mass and coupling constant) acquire thermal and topological contributions. In the case of one compactified spatial dimension at finite temperature, we find that the corrections to the mass are positive, but those to the coupling constant are negative. We discuss the possibility of triviality, i.e. that the renormalized coupling constant goes to zero at some temperature or at some radius of the compactified spatial dimension.Comment: 16 pages, plain LATE

Coarse-Graining and Renormalization Group in the Einstein Universe

The Kadanoff-Wilson renormalization group approach for a scalar self-interacting field theor generally coupled with gravity is presented. An average potential that monitors the fluctuations of the blocked field in different scaling regimes is constructed in a nonflat background and explicitly computed within the loop-expansion approximation for an Einstein universe. The curvature turns out to be dominant in setting the crossover scale from a double-peak and a symmetric distribution of the block variables. The evolution of all the coupling constants generated by the blocking procedure is examined: the renormalized trajectories agree with the standard perturbative results for the relevant vertices near the ultraviolet fixed point, but new effective interactions between gravity and matter are present. The flow of the conformal coupling constant is therefore analyzed in the improved scheme and the infrared fixed point is reached for arbitrary values of the renormalized parameters.Comment: 18 pages, REVTex, two uuencoded figures. (to appear in Phys. Rev. D15, July) Transmission errors have been correcte

Effective Lagrangian for self-interacting scalar field theories in curved spacetime

We consider a self-interacting scalar field theory in a slowly varying gravitational background field. Using zeta-function regularization and heat-kernel techniques, we derive the one-loop effective Lagrangian up to second order in the variation of the background field and up to quadratic terms in the curvature tensors. Specializing to different spacetimes of physical interest, the influence of the curvature on the phase transition is considered.Comment: 14 pages, LaTex, UTF 29

Gastric xenon trapping mimicking COPD: Recognition using an effervescent agent

Trapping of xenon 133 in the stomach due to gas swallowing can mimic xenon 133 retention in the left lower lobe due to obstructive lung disease on pulmonary ventilation/perfusion studies. In such cases, ingestion of sodium citrate-bicarbonate-simethicone crystals, which from CO 2 gas on contact with water, can distend the xenoncontaining stomach and allow clear delineation of its gastric location. This approach is useful in selected cases and may help avoid false-positive diagnoses of obstructive airways disease.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46824/1/259_2004_Article_BF00276710.pd

Oncogenic Kras-mediated cytokine CCL15 regulates pancreatic cancer cell migration and invasion through ROS

Pancreatic ductal adenocarcinoma (PDAC) is well known for its high death rate due to prompt cancer metastasis caused by cancer cell migration and invasion within the early stages of its development. Here, we reveal a new function of cytokine CCL15, namely the upregulation of PDAC cell migration and invasion. We showed increased levels of CCL15 transcripts and protein expressions in human PDAC tissue samples, as well as in cultured cell lines. Furthermore, PDAC cells also expressed CCL15 receptors, including CCR1 and CCR3. Murine PDAC cell lines and tissues strengthened this finding. The manipulation of CCL15 in metastatic Panc-1 cells through CCL15 knockdown or CCL15 neutralization decreased Panc-1 cell motility and invasiveness. In addition, treating non-metastatic BxPC-3 cells with recombinant CCL15 accelerated the cell migration of BxPC-3. A reduction in the levels of reactive oxygen species (ROS) by either N-Acetyl-L-Cysteine treatment or p22phox knockdown led to a decrease in Panc-1 cell migration and a reversed effect on recombinant CCL15-promoted BxPC-3 cell movement. Importantly, the knockdown of oncogenic Kras in Panc-1 cells abolished CCL15 protein expression and impeded cell migration without affecting PDAC cell growth. Altogether, our work elucidates an additional molecular pathway of oncogenic Kras to promote PDAC metastasis through the upregulation of cell migration and invasion by the Kras downstream CCL15, a lesser-known cytokine within the cancer research field