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Precision Medicine and Imaging

Exploitation of CD133 for the Targeted Imaging of Lethal Prostate Cancer

Paige M. Glumac, Joseph P. Gallant, Mariya Shapovalova, Yingming Li, Paari Murugan, Shilpa Gupta, Ilsa M. Coleman, Peter S. Nelson, Scott M. Dehm and Aaron M. LeBeau
Paige M. Glumac
1Department of Pharmacology, University of Minnesota Medical School, Minneapolis, Minnesota.
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Joseph P. Gallant
1Department of Pharmacology, University of Minnesota Medical School, Minneapolis, Minnesota.
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Mariya Shapovalova
1Department of Pharmacology, University of Minnesota Medical School, Minneapolis, Minnesota.
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Yingming Li
2Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.
3Departments of Laboratory Medicine and Pathology and Urology, University of Minnesota Medical School, Minneapolis, Minnesota.
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Paari Murugan
3Departments of Laboratory Medicine and Pathology and Urology, University of Minnesota Medical School, Minneapolis, Minnesota.
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  • ORCID record for Paari Murugan
Shilpa Gupta
4Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota.
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Ilsa M. Coleman
5Fred Hutchinson Cancer Research Center, Seattle, Washington.
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Peter S. Nelson
5Fred Hutchinson Cancer Research Center, Seattle, Washington.
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Scott M. Dehm
2Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.
3Departments of Laboratory Medicine and Pathology and Urology, University of Minnesota Medical School, Minneapolis, Minnesota.
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  • ORCID record for Scott M. Dehm
Aaron M. LeBeau
1Department of Pharmacology, University of Minnesota Medical School, Minneapolis, Minnesota.
2Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.
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  • For correspondence: alebeau@umn.edu
DOI: 10.1158/1078-0432.CCR-19-1659 Published March 2020
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Abstract

Purpose: Aggressive variant prostate cancer (AVPC) is a nonandrogen receptor–driven form of disease that arises in men in whom standard-of-care therapies have failed. Therapeutic options for AVPC are limited, and the development of novel therapeutics is significantly hindered by the inability to accurately quantify patient response to therapy by imaging. Imaging modalities that accurately and sensitively detect the bone and visceral metastases associated with AVPC do not exist.

Experimental Design: This study investigated the transmembrane protein CD133 as a targetable cell surface antigen in AVPC. We evaluated the expression of CD133 by microarray and IHC analysis. The imaging potential of the CD133-targeted IgG (HA10 IgG) was evaluated in preclinical prostate cancer models using two different imaging modalities: near-infrared and PET imaging.

Results: Evaluation of the patient data demonstrated that CD133 is overexpressed in a specific phenotype of AVPC that is androgen receptor indifferent and neuroendocrine differentiated. In addition, HA10 IgG was selective for CD133-expressing tumors in all preclinical imaging studies. PET imaging with [89Zr]Zr-HA10 IgG revealed a mean %ID/g of 24.30 ± 3.19 in CD133-positive metastatic lesions as compared with 11.82 ± 0.57 in CD133-negative lesions after 72 hours (P = 0.0069). Ex vivo biodistribution showed similar trends as signals were increased by nearly 3-fold in CD133-positive tumors (P < 0.0001).

Conclusions: To our knowledge, this is the first study to define CD133 as a targetable marker of AVPC. Similarly, we have developed a novel imaging agent, which is selective for CD133-expressing tumors, resulting in a noninvasive PET imaging approach to more effectively detect and monitor AVPC.

This article is featured in Highlights of This Issue, p. 979

Footnotes

  • Note: Supplementary data for this article are available at Clinical Cancer Research Online (http://clincancerres.aacrjournals.org/).

  • Clin Cancer Res 2020;26:1054–64

  • Received May 24, 2019.
  • Revision received September 21, 2019.
  • Accepted November 7, 2019.
  • Published first November 15, 2019.
  • ©2019 American Association for Cancer Research.
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Clinical Cancer Research: 26 (5)
March 2020
Volume 26, Issue 5
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Exploitation of CD133 for the Targeted Imaging of Lethal Prostate Cancer
Paige M. Glumac, Joseph P. Gallant, Mariya Shapovalova, Yingming Li, Paari Murugan, Shilpa Gupta, Ilsa M. Coleman, Peter S. Nelson, Scott M. Dehm and Aaron M. LeBeau
Clin Cancer Res March 1 2020 (26) (5) 1054-1064; DOI: 10.1158/1078-0432.CCR-19-1659

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Exploitation of CD133 for the Targeted Imaging of Lethal Prostate Cancer
Paige M. Glumac, Joseph P. Gallant, Mariya Shapovalova, Yingming Li, Paari Murugan, Shilpa Gupta, Ilsa M. Coleman, Peter S. Nelson, Scott M. Dehm and Aaron M. LeBeau
Clin Cancer Res March 1 2020 (26) (5) 1054-1064; DOI: 10.1158/1078-0432.CCR-19-1659
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