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A compartment model for optimal delivery in radioimmunotherapy (RIT) on neuroblastoma
Author(s) -
Fu Bingmei M.,
Lv Yonggang,
Cheung NaiKong V.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.756.16
Subject(s) - radioimmunotherapy , isotope , neuroblastoma , antibody , pharmacokinetics , chemistry , dissociation rate , cerebrospinal fluid , nuclear medicine , receptor , medicine , dissociation (chemistry) , immunology , biology , physics , monoclonal antibody , cell culture , quantum mechanics , genetics
RIT can effectively treat neuroblastoma when radioactive isotope‐antibodies are administered through cerebrospinal fluid (CSF). To optimize the delivery efficacy in RIT, a compartment model was developed to quantify the time‐dependent concentrations of the bound antibodies with isotopes to the receptors on tumor cells (C IAR (t)),the free antibodies with isotopes (C IA (t)), and the unbound receptors (C R (t)), under various conditions. The criteria for the optimal delivery in RIT are to maximize the area under the curve (AUC) of C IAR (t), AUC(C IAR (t)), and minimize AUC(C IA (t)). Our results showed that: 1) The association and dissociation rate coefficients of antibodies to receptors have the same effects on optimal delivery under our clinical conditions of radioactive isotope half life ~8.5 days and CSF flow rates from 5–20 ml/hr in human; 2) The change from 10 −8 M to 10 −9 M in the equilibrium dissociation constant has the most improvement in optimal delivery. In contrast, further change from 10 −10 M to 10 −12 M has only insignificant improvement; 3) The AUC(C IAR (t)) under continuous infusion has no obvious difference from that under one dose injection although C IAR (t) profiles are different; 4) If the parameter values for the dosage, CSF volume, CSF flow rate are in proportion, the rat model can be used to predict the delivery efficacy for the human. This work was supported in part by a MSKCC research grant.