Prediction of therapy tumor-absorbed dose estimates in I-131 radioimmunotherapy using tracer data via a mixed-model fit to time activity

Cancer Biother Radiopharm. 2012 Sep;27(7):403-11. doi: 10.1089/cbr.2011.1053.

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 least-squares 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / pharmacokinetics*
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacokinetics
  • Female
  • Humans
  • Lymphoma, Follicular / drug therapy
  • Lymphoma, Follicular / metabolism*
  • Lymphoma, Follicular / radiotherapy*
  • Male
  • Middle Aged
  • Models, Biological
  • Multimodal Imaging / methods
  • Positron-Emission Tomography
  • Radioimmunotherapy / methods
  • Radiotherapy Dosage
  • Tomography, Emission-Computed, Single-Photon / methods*
  • Tomography, X-Ray Computed

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • tositumomab I-131