PET-based compartmental modeling of (124)I-A33 antibody: Quantitative characterization of patient-specific tumor targeting in colorectal cancer Journal Article

Authors: Zanzonico, P.; Carrasquillo, J. A.; Pandit-Taskar, N.; O'Donoghue, J. A.; Humm, J. L.; Smith-Jones, P.; Ruan, S.; Divgi, C.; Scott, A. M.; Kemeny, N. E.; Fong, Y.; Wong, D.; Scheinberg, D.; Ritter, G.; Jungbluth, A.; Old, L. J.; Larson, S. M.
Article Title: PET-based compartmental modeling of (124)I-A33 antibody: Quantitative characterization of patient-specific tumor targeting in colorectal cancer
Abstract: Purpose: 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 124I-labeled antitumor antibodies. Methods: 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 124I-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. Results: 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. Conclusion: 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. © 2015, Springer-Verlag Berlin Heidelberg.
Keywords: unclassified drug; positron emission tomography; colorectal cancer; body weight; tumor antigen; monoclonal antibody; blood sampling; quantitative analysis; cell membrane; antibody specificity; iodine 124; pet; whole body pet; compartment model; modeling; a33; iodine-124; plasma clearance; human; article; monoclonal antibody a33; anion exchange; association rate constant
Journal Title: European Journal of Nuclear Medicine and Molecular Imaging
Volume: 42
Issue: 11
ISSN: 1619-7070
Publisher: Springer  
Date Published: 2015-10-01
Start Page: 1700
End Page: 1706
Language: English
DOI: 10.1007/s00259-015-3061-2
PROVIDER: scopus
PUBMED: 26194713
PMCID: PMC4870891
Notes: Export Date: 2 October 2015 -- Source: Scopus
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MSK Authors
  1. Yuman Fong
    751 Fong
  2. John Laurence Humm
    352 Humm
  3. Pat B Zanzonico
    261 Zanzonico
  4. Achim Jungbluth
    363 Jungbluth
  5. Gerd Ritter
    159 Ritter
  6. Shutian Ruan
    47 Ruan
  7. Steven M Larson
    834 Larson
  8. Douglas W Wong
    173 Wong
  9. Lloyd J Old
    397 Old
  10. Nancy Kemeny
    395 Kemeny