Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Idée, J.M. et al.

Idée, Port, Robert, Raynal, Prigent, Dencausse, Le Greneur, Tichkowsky, Le Lem, Bourrinet, Mugel, Benderbous, Devoldere, Bourbouze, Meyer, Bonnemain, Corot,

Preclinical profile of the monodisperse iodinated macromolecular blood pool agent P743.

RATIONALE AND OBJECTIVES: To summarize the chemical synthesis, physicochemical characterization, pharmacokinetic behavior, and biological evaluation of P743, a new macromolecular iodinated contrast medium. METHODS: The synthesis and molecular modeling of the iodinated macromolecule P743 are described. The pharmacokinetic profile was established in rabbits and rats. Acute toxicity in mice, renal tolerance in normal rabbits, and renal tolerance in uninephrectomized, dehydrated rats undergoing selective intrarenal injection was evaluated. In vitro permeability effects on isolated mastocytes and on the coagulation pathways were carried out. Computed tomography vascular imaging was performed after intravenous injection of P743 (300 mg I/kg) in rabbits and compared with the nonspecific nonionic agent iobitridol. RESULTS: P743 is a monodisperse, macromolecular iodinated contrast medium. In both rabbits and rats, P743 showed a pharmacokinetic profile consistent with that of a rapid-clearance blood-pool agent. Its diffusion through the endothelium was found to be low in vitro, thus confirming early confinement of this macromolecule, unlike nonspecific contrast media. In both species, P743 was excreted by glomerular filtration. Acute toxicity disclosed no mortality at the highest volume that could be injected into mice, leading to a median lethal dose greater than 8.9 g I/kg. Renal tolerance was found to be good in both euvolemic rabbits and uninephrectomized, dehydrated rats. No histamine or leukotriene B4 release was found on RBL-2H3 isolated mastocytes. P743 did not interfere with the coagulation pathways. Imaging experiments confirmed that P743 remains in the vascular compartment for a longer time than does iobitridol, thus allowing vascular enhancement that is twice as high as that of iobitridol in the recirculation phase. CONCLUSIONS: The pharmacokinetic and imaging profiles of P743, a new, monodisperse, macromolecular blood-pool iodinated contrast medium, were consistent with those of a rapid-clearance blood-pool agent. Its initial safety profile is satisfactory. Further experimental imaging studies are required to define the clinical interest in such molecules.[1]

References

Preclinical profile of the monodisperse iodinated macromolecular blood pool agent P743. Idée, J.M., Port, M., Robert, P., Raynal, I., Prigent, P., Dencausse, A., Le Greneur, S., Tichkowsky, I., Le Lem, G., Bourrinet, P., Mugel, T., Benderbous, S., Devoldere, L., Bourbouze, R., Meyer, D., Bonnemain, B., Corot, C. Investigative radiology. (2001) [Pubmed]

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