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Title: Applications of immunoPET: Using 124I-anti-PSCA A11 minibody for imaging disease progression and response to therapy in mouse xenograft models of prostate cancer

Journal Article · · Clinical Cancer Research

Here, prostate stem cell antigen (PSCA) is highly expressed in local prostate cancers and prostate cancer bone metastases and its expression correlates with androgen receptor activation and a poor prognosis. Here in this study, we investigate the potential clinical applications of immunoPET with the anti-PSCA A11 minibody, an antibody fragment optimized for use as an imaging agent. We compare A11 minibody immunoPET to 18F-Fluoride PET bone scans for detecting prostate cancer bone tumors and evaluate the ability of the A11 minibody to image tumor response to androgen deprivation. Osteoblastic, PSCA expressing, LAPC-9 intratibial xenografts were imaged with serial 124I-anti-PSCA A11 minibody immunoPET and 18F-Fluoride bone scans. Mice bearing LAPC-9 subcutaneous xenografts were treated with either vehicle or MDV-3100 and imaged with A11 minibody immunoPET/CT scans pre- and post-treatment. Ex vivo flow cytometry measured the change in PSCA expression in response to androgen deprivation. A11 minibody demonstrated improved sensitivity and specificity over 18F-Fluoride bone scans for detecting LAPC-9 intratibial xenografts at all time points. Finally, LAPC-9 subcutaneous xenografts showed downregulation of PSCA when treated with MDV-3100 which A11 minibody immunoPET was able to detect in vivo.

Research Organization:
Univ. of California, Los Angeles, CA (United States)
Sponsoring Organization:
USDOE
Grant/Contract Number:
SC0001220
OSTI ID:
1345504
Journal Information:
Clinical Cancer Research, Vol. 20, Issue 24; ISSN 1078-0432
Publisher:
American Association for Cancer ResearchCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 25 works
Citation information provided by
Web of Science

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Cited By (6)

Dual-Modality ImmunoPET/Fluorescence Imaging of Prostate Cancer with an Anti-PSCA Cys-Minibody journal January 2018
Aligning physics and physiology: Engineering antibodies for radionuclide delivery journal May 2018
[89Zr]A2cDb Immuno-PET of Prostate Cancer in a Human Prostate Stem Cell Antigen Knock-in (hPSCA KI) Syngeneic Model journal June 2019
Bio‐Conjugated Advanced Materials for Targeted Disease Theranostics journal March 2020
Antibody Fragment and Affibody ImmunoPET Imaging Agents: Radiolabelling Strategies and Applications journal November 2018
89 Zr-ImmunoPET companion diagnostics and their impact in clinical drug development journal March 2018

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