Leveraging PET to image folate receptor α therapy of an antibody-drug conjugate

EJNMMI Research
Christian BrandThomas Reiner

Abstract

The folate receptor α (FRα)-targeting antibody-drug conjugate (ADC), IMGN853, shows great antitumor activity against FRα-expressing tumors in vivo, but patient selection and consequently therapy outcome are based on immunohistochemistry. The aim of this study is to develop an antibody-derived immuno-PET imaging agent strategy for targeting FRα in ovarian cancer as a predictor of treatment success. We developed [89Zr]Zr-DFO-M9346A, a humanized antibody-based radiotracer targeting tumor-associated FRα in the preclinical setting. [89Zr]Zr-DFO-M9346A's binding ability was tested in an in vitro uptake assay using cell lines with varying FRα expression levels. The diagnostic potential of [89Zr]Zr-M9346A was evaluated in KB and OV90 subcutaneous xenografts. Following intravenous injection of [89Zr]Zr-DFO-M9346A (~90 μCi, 50 μg), PET imaging and biodistribution studies were performed. We determined the blood half-life of [89Zr]Zr-DFO-M9346A and compared it to the therapeutic, radioiodinated ADC [131I]-IMGN853. Finally, in vivo studies using IMG853 as a therapeutic, paired with [89Zr]Zr-DFO-M9346A as a companion diagnostic were performed using OV90 xenografts. DFO-M9346A was labeled with Zr-89 at 37 °C within 60 min and isolated in labe...Continue Reading

References

Jan 1, 1978·Journal of the National Cancer Institute·R T EaganC G Moertel
Apr 20, 2004·Advanced Drug Delivery Reviews·Hala Elnakat, Manohar Ratnam
Feb 3, 2006·International Journal of Cancer. Journal International Du Cancer·Linda E Kelemen
Mar 3, 2007·Cancer Metastasis Reviews·Marcela D'Alincourt Salazar, Manohar Ratnam
Aug 23, 2007·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Martin D ForsterAnn L Jackman
Jul 28, 2010·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Jason P HollandJason S Lewis
Mar 23, 2012·Nature Reviews. Cancer·Andrew M ScottLloyd J Old
Sep 14, 2013·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Nerissa Therese Viola-VillegasJason S Lewis
Mar 29, 2014·Annals of Oncology : Official Journal of the European Society for Medical Oncology·R T MorrisW A Harb
Apr 15, 2014·International Journal of Women's Health·Mathieu LuyckxJean-François Baurain
Jun 7, 2014·Frontiers in Oncology·Dana Olsen, Jan Trøst Jørgensen
Dec 3, 2014·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Yehuda G AssarafJoseph A Reddy
Jun 8, 2015·The Cancer Journal·Ameya D PuranikRichard P Baum
Jun 13, 2015·Annals of Oncology : Official Journal of the European Society for Medical Oncology·J A LedermannT Thigpen
Sep 24, 2015·Drug Design, Development and Therapy·Ronald L Van HeertumMichael O'Neal
Dec 22, 2015·Seminars in Nuclear Medicine·David A MankoffDaniel A Pryma
Dec 30, 2015·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Samira M SadowskiElectron Kebebew
Jun 21, 2016·Nature Communications·Carlos Pérez-MedinaThomas Reiner
Feb 15, 2017·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Christian BrandThomas Reiner
Mar 18, 2017·Nature Reviews. Drug Discovery·Alain BeckNathalie Corvaïa
Apr 1, 2014·Annals of Oncology : Official Journal of the European Society for Medical Oncology·R T MorrisW A Harb

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Citations

Mar 11, 2020·Nature Reviews. Clinical Oncology·Mariana ScarantiUdai Banerji
Feb 11, 2020·Frontiers in Oncology·Sridhar Nimmagadda, Marie-France Penet
Feb 19, 2020·Molecular Pharmaceutics·Jordan M WhiteNerissa T Viola
Mar 24, 2020·Chemical Reviews·Weijun WeiWeibo Cai
Sep 21, 2021·Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology·Namita MahadikRajkumar Banerjee

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Methods Mentioned

BETA
biopsy
xenografts
xenograft

Clinical Trials Mentioned

NCT02631876

Software Mentioned

3D
AsiPro [UNK]
Inveon research workplace

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