Multiple target-specific molecular agents for detection and image analysis of breast cancer characteristics in mice.

Breast cancer is a heterogenetic tumor at the cellular level with multiple factors and components. The inconsistent expression of molecular markers during disease progression reduces the accuracy of diagnosis and efficacy of target-specific therapy. Single target-specific imaging agents can only provide limited tumor information at one time point. In contrast, multiple target-specific imaging agents can increase the accuracy of diagnosis. The aim of this study was to demonstrate the ability of multi-agent imaging to discriminate such differences in single tumor. Mice bearing human cancer cell xenografts were tested to determine individual differences under optimal experimental conditions. Neovasculature agent (RGD peptide), tumor stromal agent (matrix metalloproteinase), and tumor cell markers (epidermal growth factor, Her-2, interleukin 11) imaging agents were labeled with reporters. 18F-Fluorodeoxyglucose was used to evaluate the tumor glucose status. Optical, X-ray, positron emission tomography, and computer tomography imaging modalities were used to determine tumor characteristics. Tumor size and imaging data demonstrated that individual differences exist under optimal experimental conditions. The target-specific agents used in the study bind to human breast cancer cell lines in vitro and xenografts in vivo. The pattern of binding corresponds to that of tumor markers. Multi-agent imaging had complementary effects in tumor detection. Multiple noninvasive imaging agents and modalities are complementary in the interrogation of unique biological information from each individual tumor. Such multi-agent approaches provide methods to study several disease components simultaneously. In addition, the imaging results provide information on disease status at the molecular level.

Multiple target-specific molecular imaging agents detect liver cancer in a preclinical model.

Liver cancer is the fifth most common cause of cancer deaths worldwide. Noninvasive diagnosis is difficult and the disease heterogeneity reduces the accuracy of pathological assays. Improvement in diagnostic imaging of specific molecular disease markers has provided hope for accurate and early noninvasive detection of liver cancer. However, all current imaging technologies, including ultrasonography, computed tomography (CT), positron emission tomography (PET), and magnetic resonance imaging, are not specific targets for detection of liver cancer. The aim of this study was to test the feasibility of injecting a cocktail of specific molecular imaging agents to noninvasively image liver cancer. The target-specific cocktail contained agents for imaging the neovasculature (RGD peptide), matrix metalloproteinase (MMP), and glucose transport ((18)F-fluorodeoxyglucose [(18)F-FDG]). Imaging studies were performed in liver cancer cells and xenograft models. The distribution of MMP at the intracellular level was imaged by confocal microscopy. RGD, MMP, and (18)F-FDG were imaged on tumor-bearing mice using PET, CT, X-ray, and multi-wavelength optical imaging modalities. Image data demonstrated that each agent bound to a specific disease target component. The same liver cancer xenograft contained multiple disease markers. Those disease markers were heterogenetically distributed in the same tumor nodule. The molecular imaging agents had different distributions in the whole body and inside the tumor nodule. All target-specific agents yielded high tumor-to-background ratios after injection. In conclusion, target-specific molecular imaging agents can be used to study liver cancer in vitro and in vivo. Noninvasive multimodal/multi-target-specific molecular imaging agents could provide tools to simultaneously study multiple liver cancer components.

The origin of the moon and the single-impact hypothesis III.

In previous papers in this series the smoothed particle hydrodynamics method (SPH) has been used to explore the conditions in which a major planetary collision may have been responsible for the formation of the Moon. In Paper II (W. Benz, W.L. Slattery, and A.G.W. Cameron 1987, Icarus 71, 30-45) it was found that the optimum conditions were obtained when the mass ratio of the impactor to the protoearth was 0.136. In the present paper we investigate the importance of the equation of state by running this optimum case several times and varying the equation of state and other related parameters. The two equations of state compared are the Tillotson (used in the previous papers) and the CHART D/CSQ ANEOS. Because of differences in these equations of state, including the fact that different types of rocks were used in association with each, it was not possible to prepare initial planetary models that were comparable in every respect, so several different simulations were necessary in which different planetary parameters were matched between the equations of state. We also used a new version of the SPH code. The results reaffirmed the previous principal conclusions: the collisions produced a disk of rocky material in orbit, with most of the material derived from the impacting object. These results indicate that the equation of state is not a critical factor in determining the amount of material thrown into orbit. This confirms the conclusions of Paper II that gravitational torques, and not pressure gradients, inject the orbiting mass. However, the way this mass is distributed in orbit is affected by the equation of state and the choice of rock material, the Tillotson equation for granite giving slightly larger mean orbital radius for the particles left in orbit than the ANEOS dunite for the same impact parameter. We also find, compared to Paper II, that in all subsequent cases the new SPH code leads to a slightly less extended prelunar accretion disk. We think this is due to the new shape adopted for the kernel. A few additional calculations were made to test the effects of increasing the impact parameter on the calculations, other parameters remaining unchanged. The motivation for this was that solar tides will have reduced the Earth-Moon angular momentum somewhat over the course of time. An increment of 6% in the angular momentum of the collision increases the amount of iron-free material in orbit and its mean orbital radius, but more than that leaves increasing amounts of iron in orbit (the iron has a small mean orbital radius). The debris from the destroyed impacting object tends to form a straight rotating bar which is very effective in transferring angular momentum. If the material near the end of the bar extends well beyond the Roche lobe, it may become unstable against gravitational clumping.

Acute respiratory failure in acute pancreatitis.

The respiratory complications of acute pancreatitis are discussed, with particular reference to the incidence, pathophysiology and management of acute respiratory distress.