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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
 [1];  [2];  [2];  [2];  [2];  [2];  [2];  [2]
  1. Univ. of California, Los Angeles, CA (United States); DOE Office of Scientific and Technical Information (OSTI)
  2. Univ. of California, Los Angeles, CA (United States)
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, Journal Name: Clinical Cancer Research Journal Issue: 24 Vol. 20; ISSN 1078-0432
Publisher:
American Association for Cancer ResearchCopyright Statement
Country of Publication:
United States
Language:
English

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Cited By (6)

Dual-Modality ImmunoPET/Fluorescence Imaging of Prostate Cancer with an Anti-PSCA Cys-Minibody journal January 2018
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
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

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