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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

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.
Authors:
 [1] ;  [1] ;  [1] ;  [1] ;  [1] ;  [1] ;  [1] ;  [1]
  1. Univ. of California, Los Angeles, CA (United States)
Publication Date:
Grant/Contract Number:
SC0001220
Type:
Accepted Manuscript
Journal Name:
Clinical Cancer Research
Additional Journal Information:
Journal Volume: 20; Journal Issue: 24; Journal ID: ISSN 1078-0432
Publisher:
American Association for Cancer Research
Research Org:
Univ. of California, Los Angeles, CA (United States)
Sponsoring Org:
USDOE
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; immunoPET; minibody; Prostate Stem Cell Antigen (PSCA); prostate cancer bone metastases; MDV-3100 (enzalutamide)
OSTI Identifier:
1345504

Knowles, Scott M., Tavare, Richard, Zettlitz, Kirstin A., Rochefort, Matthew M., Salazar, Felix B., Jiang, Ziyue Karen, Reiter, Robert E., and Wu, Anna M.. Applications of immunoPET: Using 124I-anti-PSCA A11 minibody for imaging disease progression and response to therapy in mouse xenograft models of prostate cancer. United States: N. p., Web. doi:10.1158/1078-0432.ccr-14-1452.
Knowles, Scott M., Tavare, Richard, Zettlitz, Kirstin A., Rochefort, Matthew M., Salazar, Felix B., Jiang, Ziyue Karen, Reiter, Robert E., & Wu, Anna M.. Applications of immunoPET: Using 124I-anti-PSCA A11 minibody for imaging disease progression and response to therapy in mouse xenograft models of prostate cancer. United States. doi:10.1158/1078-0432.ccr-14-1452.
Knowles, Scott M., Tavare, Richard, Zettlitz, Kirstin A., Rochefort, Matthew M., Salazar, Felix B., Jiang, Ziyue Karen, Reiter, Robert E., and Wu, Anna M.. 2014. "Applications of immunoPET: Using 124I-anti-PSCA A11 minibody for imaging disease progression and response to therapy in mouse xenograft models of prostate cancer". United States. doi:10.1158/1078-0432.ccr-14-1452. https://www.osti.gov/servlets/purl/1345504.
@article{osti_1345504,
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},
author = {Knowles, Scott M. and Tavare, Richard and Zettlitz, Kirstin A. and Rochefort, Matthew M. and Salazar, Felix B. and Jiang, Ziyue Karen and Reiter, Robert E. and Wu, Anna M.},
abstractNote = {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.},
doi = {10.1158/1078-0432.ccr-14-1452},
journal = {Clinical Cancer Research},
number = 24,
volume = 20,
place = {United States},
year = {2014},
month = {10}
}