NR AXYC
AU Urayama,A.; Morales,R.; Soto,C.
TI Whole-body Biodistribution and Tissue Uptake Kinetics of PrPsc in the Initial Phase of the Infection
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Epidemiology, Risk Assessment and Transmission P04.73
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB
Although prion diseases have been a public health concern for decades, the lack of knowledge about the pharmacokinetics and biodistribution of prions complicates the risk assessment. In our prior studies, we found that the level of PrPsc in blood was undetectable several weeks after inoculation, then it became detectable during the early pre-symptomatic phase, disappeared from blood right before the symptomatic phase and raised to its highest at the clinical stage of the disease. These data suggest that there are several stages of the movement of PrPsc in the body during the progression of the disease. The aim of the current study was to analyze the biodisribution and tissue uptake kinetics of PrPsc in the initial phase of the infection in mice.
After an intravenous injection of [131I]PrPsc (together with [125I]albumin as a vascular space marker), the levels of [131I]PrPsc in serum decreased biphasically with time, whereas albumin levels did not significantly change during the course of the experiment. Elimination half-lives of [131I]PrPsc and [125I]albumin were 3.44 ± 0.42 and 17.6 ± 8.6 hr, respectively. These results suggest that the level of [131I]PrPsc in serum 24 hr after the injection is less than 1 % of the injected dose (ID). The rate for albumin was consistent with previous reports. The volumes of distribution for [131I]PrPsc (3.34 ± 0.16 ml) suggest that PrPsc was well distributed in the extracellular space in the body, whereas the majority of albumin was in the serum space. [131I]PrPsc showed higher systemic clearance rates than that of [125I]albumin. The uptake of [131I]PrPsc was also investigated in various tissues. The quantity of PrPsc taken up by brain was around 0.2 %ID, indicating that the protein can penetrate across the blood-brain barrier with a medium efficiency compared to other proteins. The higher levels of [131I]PrPsc were found in liver, spleen, kidney, lung, heart, and skeletal muscle when compared to the levels in the brain. Interestingly, TCAprecipitable [131I]PrPsc was clearly detected in urine. These results provide a fundamental pharmacokinetic characterization of PrPsc in animals that may be relevant to estimate tissue risks, mechanisms of prion neuroinvassion and to develop novel therapeutic strategies.
AD A. Urayama, R. Morales, C. Soto, University of Texas Medical Branch, USA
SP englisch
PO Schottland