Prediction of Therapy Tumor-Absorbed Dose Estimates in I-131 Radioimmunotherapy Using Tracer Data Via a Mixed-Model Fit to Time Activity

Abstract

Background: For individualized treatment planning in radioimmunotherapy (RIT), correlations must be established between tracer-predicted and therapy-delivered absorbed doses. The focus of this work was to investigate this correlation for tumors. Methods: The study analyzed 57 tumors in 19 follicular lymphoma patients treated with I-131 tositumomab and imaged with SPECT/CT multiple times after tracer and therapy administrations. Instead of the typical leastsquares fit to a single tumor's measured time-activity data, estimation was accomplished via a biexponential mixed model in which the curves from multiple subjects were jointly estimated. The tumor-absorbed dose estimates were determined by patient-specific Monte Carlo calculation.Results: The mixed model gave realistic tumor time-activity fits that showed the expected uptake and clearance phases even with noisy data or missing time points. Correlation between tracer and therapy tumor-residence times (r = 0.98; p < 0.0001) and correlation between tracer-predicted and therapy-delivered mean tumor-absorbed doses (r = 0.86; p < 0.0001) were very high. The predicted and delivered absorbed doses were within -25% (or within -75 cGy) for 80% of tumors. Conclusions: The mixed-model approach is feasible for fitting tumor time-activity data in RIT treatment planning when individual least-squares fitting is not possible due to inadequate sampling points. The good correlation between predicted and delivered tumor doses demonstrates the potential of using a pretherapy tracer study for tumor dosimetry-based treatment planning in RIT.

Tumor-Absorbed Dose Predicts Progression-Free Survival Following 131I-Tositumomab Radioimmunotherapy

“…The robust correlation shown here between tracer-predicted and therapy-delivered mean tumor-absorbed doses (with n = 124) is of much significance for treatment planning and has been demonstrated previously for a smaller sample size (13). The correlation between 2-mo tumor shrinkage and the initial tumor shrinkage during tracer imaging was also evaluated because this quantity can be determined before therapy, but the correlation was not significant.…”

VIDA: A Voxel-Based Dosimetry Method for Targeted Radionuclide Therapy Using Geant4

“…In comparison, the calculation of the mean tumor-absorbed dose using DPM involves a piecewise integration of the absorbed dose rates over three time periods using a mixed model fit. 40 These varying approaches may account for the discrepancies in tumor dose, even though the differences in tumor absorbeddose rates between the two simulations were less than 2%.…”

MIRD Pamphlet No. 24: Guidelines for Quantitative 131I SPECT in Dosimetry Applications

“…If a relatively large target volume with negligible partial-volume effects is used to determine the calibration factor, partial-volume correction is needed when using this calibration to quantify activity in small structures. A further refinement that has been shown to be significant for 131 I and in posttracer versus posttherapy imaging is a counting rate–dependent calibration factor (16). …”

“…SPECT projection data corresponding to posttherapy patient imaging were corrected for camera dead time using a paralyzable model and the dead-time constant for the system, previously determined to be 2.5 µs (16). In this case, the true projection counting rate, n , was determined iteratively on the basis of the measured counting rate, m , using the relationship m = n e − n τ , where τ is the dead-time constant (23).…”