Methodological Evaluation of Renal Time-integrated Activity Coefficient Calculated using Trapezoidal Method and Non-linear Mixed-Effects Modeling in [177Lu]Lu-DOTA-TATE Therapy

I. Budiansah, D. Hardiansyah

Abstract


This study aimed to compare renal Time-Integrated Activity Coefficients (TIACs) in [177Lu]Lu-DOTA-TATE therapy calculated using the trapezoidal method and Non-Linear Mixed-Effects (NLME) modeling. Renal biokinetic data of [177Lu]Lu-DOTA-TATE were collected from ten patients with neuroendocrine tumors. SPECT/CT imaging was performed between days 1 and 7 after-injection. The full trapezoidal method and the trapezoidal method combined with monoexponential decay from last time point was implemented in R version 4.5. In addition, the TIACs calculated using a bi-exponential function derived from NLME modeling implemented in NONMEM software version 7.6.0 was also analyzed. TIACs derived from bi-exponential fit function with NLME modeling were considered as reference TIACs (rTIACs). The performance of trapezoidal method in estimating the TIACs was evaluated using Relative Deviations (RDs) from the rTIACs. Full trapezoidal method systematically underestimated the rTIACs with mean of RD of -17% while the trapezoidal method with monoexponential decay from the last time point systematically overestimated the rTIACs with mean RD of 30%. Therefore, the implementation of appropriate model-based fit functions is recommended, as relying on an inadequate method may result in systematic over- or underestimation of the TIAC values.

Keywords


NLME Modeling, Trapezoidal Method, TIAC, NONMEM

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DOI: https://doi.org/10.55981/aij.2026.1881

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