Method to quantify tail vein injection technique in small animals

摘要

Injection errors, which are often not readily recognized, can greatly impact the outcome of a pre-clinical research study. As a result, unrecognized misadministration of test compounds can render a high cost to the biomedical community. In this report, we propose six criteria for a reagent designed to assess tail vein injection technique in small animals and suggest a reagent, colloidal gold labeled with the stable isotope Au-197, that satisfies these criteria, thereby describing and validating for the first time a method to quantify technical compliance in tail vein injections. In an application of this reagent, we show the degree of variation experienced by technologists performing tail vein injection procedures in mice. In this study, mice were manually restrained and received an injection in the tail vein. One hour after injection, the mice were euthanized, various organs including the tail (the site of the injection) were collected, and their gold content was quantified by neutron activation. The three experienced animal technologists in the study were tested for tail vein injection proficiency in 30 mice. Prior to the study, the supervisor stated that a misinjection occurs when more than 10% of the intended volume remains in the tail. In light of this criterion, 12 of the 30 injections were misadministered: two with technologist 1, three with technologist 2, and seven with technologist 3. Although she was able to correctly rank the injection skills of the three technologists used in this experiment, i.e., technologist 1 and 2 more better skilled than technologist 3, the supervisor greatly underestimated the extent and degree of injection failures for the procedure. The results of the study illustrate the potential problems associated with the technical compliance with this common laboratory procedure and suggest that there is a need to validate injection methods and a need to monitor technical competence. Application of reagents similar to colloidal gold and the methods presented will facilitate the development of improved methods of teaching injection technique and monitoring technical quality in the laboratory setting.