PET-based compartmental modeling of I-124-A33 antibody: quantitative characterization of patient-specific tumor targeting in colorectal cancer Academic Article uri icon

abstract

  • The molecular specificity of monoclonal antibodies (mAbs) directed against tumor antigens has proven effective for targeted therapy of human cancers, as shown by a growing list of successful antibody-based drug products. We describe a novel, nonlinear compartmental model using PET-derived data to determine the "best-fit" parameters and model-derived quantities for optimizing biodistribution of intravenously injected (124)I-labeled antitumor antibodies.As an example of this paradigm, quantitative image and kinetic analyses of anti-A33 humanized mAb (also known as "A33") were performed in 11 colorectal cancer patients. Serial whole-body PET scans of (124)I-labeled A33 and blood samples were acquired and the resulting tissue time-activity data for each patient were fit to a nonlinear compartmental model using the SAAM II computer code.Excellent agreement was observed between fitted and measured parameters of tumor uptake, "off-target" uptake in bowel mucosa, blood clearance, tumor antigen levels, and percent antigen occupancy.This approach should be generally applicable to antibody-antigen systems in human tumors for which the masses of antigen-expressing tumor and of normal tissues can be estimated and for which antibody kinetics can be measured with PET. Ultimately, based on each patient's resulting "best-fit" nonlinear model, a patient-specific optimum mAb dose (in micromoles, for example) may be derived.

authors

  • Zanzonico, P
  • Carrasquillo, JA
  • Pandit-Taskar, N
  • O'Donoghue, JA
  • Humm, JL
  • Smith-Jones, P
  • Ruan, S
  • Divgi, C
  • Scott, AM
  • Kemeny, NE
  • Fong, Y
  • Wong, D
  • Scheinberg, D
  • Ritter, G
  • Jungbluth, A
  • Old, LJ
  • Larson, SM

publication date

  • 2015