The CONRAD approach to biokinetic modeling of DTPA decorporation therapy.

Diethylene Triamine Pentaacetic Acid (DTPA) is used for decorporation of plutonium because it is known to be able to enhance its urinary excretion for several days after treatment by forming stable Pu-DTPA complexes. The decorporation prevents accumulation in organs and results in a dosimetric benefit, which is difficult to quantify from bioassay data using existing models. The development of a biokinetic model describing the mechanisms of actinide decorporation by administration of DTPA was initiated as a task in the European COordinated Network on RAdiation Dosimetry (CONRAD). The systemic biokinetic model from Leggett et al. and the biokinetic model for DTPA compounds of International Commission on Radiological Protection Publication 53 were the starting points. A new model for biokinetics of administered DTPA based on physiological interpretation of 14C-labeled DTPA studies from literature was proposed by the group. Plutonium and DTPA biokinetics were modeled separately. The systems were connected by means of a second order kinetics process describing the chelation process of plutonium atoms and DTPA molecules to Pu-DTPA complexes. It was assumed that chelation only occurs in the blood and in systemic compartment ST0 (representing rapid turnover soft tissues), and that Pu-DTPA complexes and administered forms of DTPA share the same biokinetic behavior. First applications of the CONRAD approach showed that the enhancement of plutonium urinary excretion after administration of DTPA was strongly influenced by the chelation rate constant. Setting it to a high value resulted in a good fit to the observed data. However, the model was not yet satisfactory since the effects of repeated DTPA administration in a short time period cannot be predicted in a realistic way. In order to introduce more physiological knowledge into the model several questions still have to be answered. Further detailed studies of human contamination cases and experimental data will be needed in order to address these issues. The work is now continued within the European Radiation Dosimetry Group, EURADOS.

Physiology-based modelling in radiation research: the biokinetics of plutonium.

For many years, the biokinetics of radioactive substances was calculated on the basis of mathematical criteria only. Biokinetic compartments in most cases did not correspond to anatomically defined distribution areas in an organism but were operational values. However, the quality of the resulting models depends on how accurately their assumptions reflect reality. Ideally, a biokinetic model develops which reproduces reality. In the past few years, this need has resulted increasingly in physiological operational sequences being modelled in realistic anatomical structures of the body along with physicochemical parameters. In this study, an estimate of the biokinetic operational sequence after an incorporation of plutonium is made similar to the pharmacokinetics of a substance showing comparable chemical and physiological behaviours in the body. These behaviours are found for metals, iron and aluminium. Thus, comparison of the biokinetics of plutonium with the pharmacokinetics of aluminium results in some commonalities and some differences. A new model with physiological compartments for plutonium is presented on the basis of the biokinetics of aluminium.

Photo-chemically patterned polymer surfaces for controlled PC-12 adhesion and neurite guidance.

The in vitro assembling of cellular networks offering control over cell positions and connectivities by patterned culture substrates is a valuable tool for neuroscience research and other applications in cell biology. We developed a versatile technique based on polymer surface modification which allows the patterning of different cell lines for advanced tissue engineering, among them are Pheochromocytoma cells (PC-12). In contrast to other techniques applied for surface patterning, the presented photo patterning by deep UV irradiation is applicable to the widely used cell culture substrate material polystyrene (PS) and should be easily performed in most laboratories. Irradiation of polystyrene with UV radiation of lambda = 185 nm yields mainly carboxyl groups at the polymer surface which can be used to control the spontaneous competitive protein adsorption from serum containing culture media [Welle A, Gottwald E. UV-based patterning of polymeric substrates for cell culture applications. Biomed. Microdev. 2002;4:33-41] or to serve as defined coupling sites for controlled protein/peptide immobilization. Extending our previous studies on patterning hepatoma cells and fibroblasts via spatially defined plasma protein adsorption, we here describe an advanced application to produce patterns of cell repellent albumin domains and cell attractive laminin regions for the patterning of Pheochromocytoma cells.