ABSTRACT
The technique of whole body autoradiography (WBA) was introduced in 1954 by Sven Ullberg, in Upsala, Sweden. WBA involves the cryosectioning of whole animals such as mice, rats, rabbits and monkeys and was developed to study the distribution of compounds in the intact animal’s body. In the early days, cryosectioning was performed by technicians dressed in fur coats in a cold room maintained at –15 °C using a hand-driven sledge microtome (Ullberg, 1954, 1958). Today, the technique has been refined substantially, and highly specialised equipment has been designed for all aspects of WBA techniques. WBA was developed in part to overcome the technical problems encountered in traditional methods of studying compound distribution. Many compounds are soluble in water or other liquids used in the histological preparation of tissue specimens and may therefore be extracted from the specimen during processing. WBA allows for the fixation of the compound in the intact animal by freezing, thereby preventing any tissue preservation liquids from coming into contact with the test compound. As such, the localisation of the compound is preserved (Ullberg, 1977). WBA has many applications, but its most frequent use is to generate comprehensive information about the distribution 192pattern of new drug candidates. For this application, WBA data are used to support histopathology data from toxicity testing, and to generate radiolabelled dose estimates for human studies. The technique may also be used for a variety of other applications, including the identification of target tissues for a test compound, receptor identification, to investigate blood–brain barrier or placental permeability, or to generate samples for micro-autoradiographic studies.
