Early distribution of radioactive liposomes and scrapie infectivity in mouse tissues following administration by different routes

Abstract

Mice were injected with 99mtechnetium-labelled liposomes or with a standard homogenate of scrapie-affected brain. Four different routes of injection were used, intracerebral (i.c.), intravenous (i.v.), intraperitoneal (i.p.) and subcutaneous (s.c.). Blood and a range of other tissues were removed between 5 min and several hours after injection. The tissues included spleen and salivary gland in which appreciable agent replication (or at least accumulation) is known to occur and, liver where replication of scrapie agent does not occur. Within 30 min of injection by any of the four routes used, radioactivity, and infectivity were detected in tissues remote from the site of injection. The distribution of radioactivity in various tissues was similar to that of infectious scrapie agent, but in both cases it occurred much more rapidly after i.v. injection than after injection by the i.p. or s.c. route. It is suggested that the 1000-fold reduced efficiency of scrapie infection by the s.c. route, compared to the i.v. route, is related to the extensive localisation of inoculum at the site of injection. Despite the relatively high efficiency of infection of the i.v. route, much of the detectable agent is taken up by liver where the agent does not replicate. It is concluded that only a very small proportion of the agent injected i.v. (and presumably by other routes) is involved in establishing scrapie infection of mice.