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Eur J Nucl Med Mol Imaging. 2015 Oct;42(11):1700-1706. doi: 10.1007/s00259-015-3061-2. Epub 2015 Jul 21.

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

Author information

1
Department of Medical Physics, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10021, USA. zanzonip@mskcc.org.
2
Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
3
Department of Medical Physics, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10021, USA.
4
Departments of Psychiatry and Radiology, Stony Brook School of Medicine, Stony Brook, NY, USA.
5
Columbia University Medical Center, New York, NY, USA.
6
Olivia Newton-John Cancer Research Institute, La Trobe University, Melbourne, Australia.
7
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
8
Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
9
Department of Surgery, City of Hope, Duarte, CA, USA.
10
Ludwig Institute for Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

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 (124)I-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 (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.

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.

PMID:
26194713
PMCID:
PMC4870891
DOI:
10.1007/s00259-015-3061-2
[Indexed for MEDLINE]
Free PMC Article

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