Using a Single Parameter to Describe Time–Activity Curves

Abstract

Time-activity uptake curves [u(t) in % injected dose per gram of tissue] may be described by different--often complicated--functional forms. Because of the need to readily compare sequences of engineered radiopharmaceuticals, it is efficient to use mean residence time (MRT) as a one-parameter descriptor. In applying this computation to a sequence of five cognate anti-carcinoembryonic antigen (CEA) antibodies, it was found that the intact form had the longest MRT in the blood with the other four cognates having values less by approximately a factor of 10 or more. This difference probably follows from the lack of an intact Fc segment on the latter engineered molecules. MRT values for a sequence of six scFv-Fc engineered fragments demonstrated that the double mutant had the shortest blood residence time--30-fold less compared with the wild type. Whereas it is not possible to directly apply the MRT to nonbolus (tumor or organ) curves, a residence time (τ) may be assigned using the uptake function. Using τ, it was found that the intact (natural) form of the anti-CEA cognate set had the longest time at the tumor site in the human xenograft model in nude mice. The MRT and τ concept are proposed to also allow comparison of possible relative blood and tissue exposures, respectively, for cognate sets of unlabeled engineered antibodies used to treat malignancies although no data are yet available in the literature for this application.