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

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
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-84940726197&partnerID=40&md5=04389002f4a8439d3d6f705d1e61da34
Notes:	Export Date: 2 October 2015 -- Source: Scopus