Krauser, Joel (2013) A perspective on tritium versus carbon-14: ensuring optimal label selection in pharmaceutical research and development. Journal of Labelled Compounds and Radiopharmaceuticals. ISSN 0362-4803

Abstract

Tritium (3H) and carbon-14 (14C) labels applied in pharmaceutical research and development each offer their own distinctive advantages and disadvantages coupled with benefits and risks. The advantages of 3H have a higher specific activity, shorter half-life that allows more manageable waste remediation, lower material costs, and often more direct synthetic routes. The advantages of 14C offer certain analytical benefits and less potential for label loss.

Although 3H labels offer several advantages, they might be overlooked as a viable option because of the concerns about its drawbacks. A main drawback often challenged is metabolic liability. These drawbacks, in some cases, might be overstated leading to underutilization of a perfectly viable option. As a consequence, label selection may automatically default to 14C, which is a more conservative approach. To challenge this ‘14C-by-default’ approach, pharmaceutical agents with strategically selected 3H-labeling positions based on non-labeled metabolism data have been successfully implemented and evaluated for 3H loss.

From in-house results, the long term success of projects clearly would benefit from a thorough, objective, and balanced assessment regarding label selection (3H or 14C). This assessment should be based on available project information and scientific knowledge. Important considerations are project applicability (preclinical and clinical phases), synthetic feasibility, costs, and timelines.

Item Type:	Article
Keywords:	tritium;carbon-14;3H;14C;isotope;label selection;pharmaceutical research and development;tritiated water;metabolic stability;metabolic switching;radiolabel
Date Deposited:	13 Oct 2015 13:13
Last Modified:	13 Oct 2015 13:13
URI:	https://oak.novartis.com/id/eprint/10019