Targeting of radiolabeled J591 antibody to PSMA-expressing tumors: optimization of imaging and therapy based on non-linear compartmental modeling

EJNMMI Research
Edward K FungJoseph Osborne

Abstract

We applied a non-linear immunokinetic model to quantitatively compare absolute antibody uptake and turnover in subcutaneous LNCaP human prostate cancer (PCa) xenografts of two radiolabeled forms of the humanized anti-prostate-specific membrane antigen (PSMA) monoclonal antibody J591 ((124)I-J591 and (89)Zr-J591). Using the model, we examined the impact of dose on the tumor and plasma positron emission tomography (PET)-derived time-activity curves. We also sought to predict the optimal targeting index (ratio of integrated-tumor-to-integrated-plasma activity concentrations) for radioimmunotherapy. The equilibrium rates of antibody internalization and turnover in the tumors were derived from PET images up to 96 h post-injection using compartmental modeling with a non-linear transfer rate. In addition, we serially imaged groups of LNCaP tumor-bearing mice injected with (89)Zr-J591 antibody doses ranging from antigen subsaturating to saturating to examine the suitability of using a non-linear approach and derived the time-integrated concentration (in μM∙hours) of administered tracer in tumor as a function of the administered dose of antibody. The comparison of (124)I-J591 and (89)Zr-J591 yielded similar model-derived values of the t...Continue Reading

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Citations

Feb 15, 2018·Diagnostics·Nat P LenzoJ Harvey Turner
Mar 10, 2018·The AAPS Journal·Ingrid J G BurvenichAndrew M Scott
May 24, 2017·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Joseph R OsborneNaga Vara Kishore Pillarsetty
Jun 21, 2020·International Journal of Molecular Sciences·Joon-Kee YoonSu-Jin Lee
Jan 21, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Krishan Kumar, Arijit Ghosh
Jul 11, 2020·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Luis David Jiménez-FrancoPeter Kletting
Aug 10, 2021·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Sergio Muñoz VázquezKlaus Schomäcker
Mar 24, 2020·Chemical Reviews·Weijun WeiWeibo Cai
Jul 23, 2020·Current Pharmaceutical Design·Hooman YariVibhudutta Awasthi
Apr 24, 2018·Molecular Pharmaceutics·Sarah M ChealJorge A Carrasquillo

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Methods Mentioned

BETA
xenograft
FCS
saturation binding
xenografts

Software Mentioned

ASIPro [UNK]
SAAM II

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