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Published on: September 3, 2013
Exploitation of CD133 for the Targeted Imaging of Lethal Prostate Cancer
Paige M Glumac1, Joseph P Gallant1, Mariya Shapovalova1
1Department of Pharmacology, University of Minnesota Medical School, Minneapolis, Minnesota.
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.
Insights
Researchers identified CD133 as a target for aggressive variant prostate cancer (AVPC). A novel imaging agent, HA10 IgG, successfully detected CD133-positive tumors using PET imaging, offering a new way to monitor this difficult-to-treat cancer.
Area of Science:
- Oncology
- Molecular Imaging
- Biomarker Discovery
Background:
- Aggressive variant prostate cancer (AVPC) is a treatment-resistant form of the disease.
- Current imaging methods struggle to accurately detect AVPC metastases.
- Limited therapeutic options exist for AVPC patients.
Purpose of the Study:
- To investigate CD133 as a targetable cell surface antigen in AVPC.
- To evaluate the imaging potential of a CD133-targeted antibody (HA10 IgG).
- To develop a novel PET imaging approach for AVPC detection and monitoring.
Main Methods:
- Microarray and immunohistochemistry (IHC) were used to assess CD133 expression in AVPC.
- HA10 IgG was tested in preclinical models using near-infrared and PET imaging.
- PET imaging utilized [89Zr]Zr-HA10 IgG to quantify tumor uptake in CD133-positive and negative lesions.
Main Results:
- CD133 is overexpressed in a specific, aggressive, neuroendocrine phenotype of AVPC.
- HA10 IgG demonstrated selectivity for CD133-expressing tumors in preclinical studies.
- PET imaging with [89Zr]Zr-HA10 IgG showed significantly higher uptake in CD133-positive metastatic lesions compared to negative lesions (P = 0.0069).
Conclusions:
- CD133 is identified as a targetable marker for aggressive variant prostate cancer.
- A novel imaging agent, HA10 IgG, enables noninvasive PET imaging of CD133-expressing AVPC.
- This approach offers a new method for detecting and monitoring AVPC, addressing a critical unmet need.
