title: 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 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.
authors.affiliation: Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan 48109, USA. mjschipp@umich.edu
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Schipper
authors.forename: Kenneth F
authors.initials: KF
authors.lastname: Koral
authors.forename: Anca M
authors.initials: AM
authors.lastname: Avram
authors.forename: Mark S
authors.initials: MS
authors.lastname: Kaminski
authors.forename: Yuni K
authors.initials: YK
authors.lastname: Dewaraja
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D008224:Lymphoma, Follicular / Q000188:drug therapy / Q000378:metabolism* / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D064847:Multimodal Imaging / Q000379:methods; D049268:Positron-Emission Tomography; D016499:Radioimmunotherapy / Q000379:methods; D011879:Radiotherapy Dosage; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*; D014057:Tomography, X-Ray Computed
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; C119496:tositumomab I-131