An International Study of Factors Affecting Variability of Dosimetry Calculations, Part 4: Impact of Fitting Functions in Estimated Absorbed Doses.

Individualized radiopharmaceutical therapies guided by patient-specific absorbed dose (AD) assessments using nuclear medicine imaging have the potential to improve both efficacy and safety. Understanding sources of variability in AD calculations is critical for standardization. The Society of Nuclear Medicine and Molecular Imaging Dosimetry Task Force launched the Lu Dosimetry Challenge to evaluate variability across steps within the dosimetry workflow. This work aimed to assess the variability in ADs due to different fitting and integration methods. Anonymized datasets from 2 patients treated with Lu-DOTATATE, including serial SPECT/CT scans, segmented organs and lesions, and time-integrated activity maps, were made available online. Participants were invited to perform dosimetry calculations and submit their results using standardized submission spreadsheets. Fitting approaches were categorized, and relative AD variability was analyzed using the quartile coefficient of dispersion and interquartile range. The variability in AD due to the fitting step for patient A's kidneys was less than 1%. In contrast, patient B's kidneys showed higher variability, with values below 10%. Lesions exhibited more variability in fitting than did kidneys, with variability within 25%. The contribution of variability caused by fitting and integration is small for healthy organs. By following recommendations such as selection of appropriate functions, pharmacokinetic modeling, and sanity checks, this variability can be further reduced.