Monday, October 15, 2012 1:34:17 PM
ImmunoPET imaging of phosphatidylserine in pro-apoptotic therapy treated tumor models
Nuclear Medicine and Biology
Annie Ogasawara 1, Jeff N. Tinianow 1, Alexander N. Vanderbilt, Herman S. Gill, Sharon Yee, Judith E. Flores,
Simon-Peter Williams, Avi Ashkenazi, Jan Marik
Genentech Research and Early Development (gRED), Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, USA
http://www.sciencedirect.com/science/article/pii/S0969805112002302
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ABSTRACT
An immunoPET imaging probe for the detection of phosphatidylserine was developed and tested in animal
models of human cancer treated with pro-apoptotic therapy. We hypothesized that the relatively long plasma
half-life of a probe based on a full-length antibody coupled with a residualizing radionuclide would be able to
catch the wave of drug-induced apoptosis and lead to a specific accumulation in apoptotic tumor tissue.
Methods: The imaging probe is based on a 89Zr-labeled monoclonal antibody PGN635 targeting
phosphatidylserine. The probe was evaluated pre-clinically in four tumor xenograft models: one studied
treatment with paclitaxel to trigger the intrinsic apoptotic pathway, and three others interrogated treatment
with an agonistic death-receptor monoclonal antibody to engage the extrinsic apoptotic pathway.
Results: High accumulation of 89Zr-PGN635 was observed in treated tumors undergoing apoptosis reaching 30
%ID/g and tumor-to-blood ratios up to 13. The tumor uptake in control groups treated with vehicle or imaged
with a non-binding antibody probe was significantly lower.
Conclusions: The results demonstrate the ability of 89Zr-PGN635 to image drug-induced apoptosis in animal
models and corroborate our hypothesis that radiolabeled antibodies binding to intracellular targets
transiently exposed on the cell surface during apoptosis can be employed for detection of tumor response
to therapy.
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Note this is a different imaging agent than used in the imaging trial, which uses 124I-PGN650
http://www.clinicaltrials.gov/ct2/show/NCT01632696?term=bavituximab+OR+Peregrine&recr=Open&rank=5
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