Effect of different radiopharmaceutical drug to the performance of translation methods of TIACs from mice to human

The aim of this study was to investigate the effect of different radiopharmaceutical drugs on the performance of translation method of time-integrated activity coefficient (TIAC) from mice to humans. ¹⁷⁷Lu-DOTA-Trastuzumab (Tras) percentage of injected dose (%ID) in Swiss Webster mice at 1, 2, 3, 4, 24, and 48 hours p.i was used to fit the parameters of the five Sum of Exponential (SOE) functions. Goodness of fit criteria, i.e graph visualization, coefficient of variation (CV<50%), and Correlation Matrix (−0.8 ≤ CM_i,j ≥ 0.8), and Akaike Information Criterion (AICc) were used to select the best function then the function was integrated to determine the TIACs value. Five translation methods, i.e. no scaling (NS), mass scaling (MS), time scaling (TS), time-mass scaling (TMS), and allometric scaling (AS) were used to translate the TIACs in mice to human for liver and kidneys. The relative deviations (RDs) of the predicted TIACs in humans from each translation method to the best translation method suggested in Beykan et al study, i.e. TS, were analyzed. The effects of the radiopharmaceutical drugs, i.e. Tras and JR11, to the performance of each translation method i were calculated as $Δi=(RDiTras−RDiJR11)$⁠. As a result, the Δ are 12%(NS); 2%(MS); 2,9%(TMS); and 3,3%(AS) for kidneys and 45,2%(NS); 13,4%(MS); 13,8%(TMS); and 23,5%(AS) for liver. In general, the Δ values are less than 15% except for the NS and AS methods in the liver. It concludes that each method yields totally different prediction from another methods that the best translation method is important for each radiopharmaceutical drugs.