Related Experiment Video
Updated: May 19, 2026
Induction of Invasive Transitional Cell Bladder Carcinoma in Immune Intact Human MUC1 Transgenic Mice: A Model for Immunotherapy Development
Published on: October 30, 2013
Glycoprotein Mucin 13 Expression as a Theranostic Target in Colorectal Cancer
Aiko Yamaguchi1, Ryan P Coll2, Jianbo Wang2
1Radiopharmaceuticals for Advanced Diagnostic Imaging and Therapy R&D Platform, Therapeutics Discovery Division, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Purpose:
The high mortality associated with metastatic colorectal cancer (mCRC) illuminates an unmet need for innovative therapeutic modalities. Radiopharmaceutical therapy (RPT) offers a potent, molecular-scale approach for managing and treating cancers with distant micrometastases. However, its clinical use in mCRC remains an unrealized opportunity. We have therefore identified the transmembrane glycoprotein mucin 13 (MUC13) as a promising antigen for developing a targeted RPT and have undertaken preclinical evaluation of its potential by utilizing a monoclonal antibody tool representative of a future class of translatable therapeutics.
Experimental Design:
The immunoreactivity and transcriptome of patients with colorectal cancer (n = 72 primary, 100 liver metastases) were characterized using annotated clinical datasets. Preclinical assessment of MUC13 as an RPT target for mCRC was then performed in mice using a monoclonal MUC13-targeted antibody C14 labeled with either zirconium-89 for positron emission tomography (PET) measurement of mCRC-associated MUC13 density or terbium-161 for targeted RPT.
Results:
Strong MUC13 immunoreactivity was observed in ∼70% of mCRC and was inversely correlated with overall survival (P < 0.01). MUC13 levels were visualized by PET and agreed with immunohistochemically determined antigen presence. Furthermore, MUC13-targeted RPT exhibited in vivo proof-of-concept efficacy and enhanced survival in preclinical colorectal cancer models. Resulting imaging, therapeutic, and pathologic analyses elucidated relationships between target density, therapeutic outcome, and a potential genetic signature.
Conclusions:
MUC13-targeted RPT response was not only associated with radiopharmaceutical accumulation but also seemed to be balanced by DNA damage repair gene expression, suggesting a potential sensitivity signature that could complement a future clinical theranostic approach in MUC13-positive mCRC.
Insights
Metastatic colorectal cancer (mCRC) shows high mortality. Mucin 13 (MUC13)-targeted radiopharmaceutical therapy (RPT) shows promise for mCRC treatment, with preclinical studies demonstrating efficacy and improved survival.
Area of Science:
- Oncology
- Nuclear Medicine
- Molecular Imaging
Background:
- Metastatic colorectal cancer (mCRC) has high mortality, necessitating novel therapies.
- Radiopharmaceutical therapy (RPT) offers targeted treatment for micrometastases.
- MUC13 is identified as a potential therapeutic target for mCRC.
Purpose of the Study:
- To evaluate Mucin 13 (MUC13) as a target for RPT in mCRC.
- To assess the preclinical efficacy of MUC13-targeted RPT using a monoclonal antibody.
Main Methods:
- Characterized MUC13 immunoreactivity and transcriptome in CRC patient samples (n=72 primary, 100 liver metastasis).
- Utilized a MUC13-targeted antibody (C14) labeled with 89Zr for PET imaging and 161Tb for RPT in preclinical mCRC mouse models.
Main Results:
- ~70% of mCRCs exhibited strong MUC13 immunoreactivity, inversely correlating with survival (P<0.01).
- PET imaging confirmed MUC13 expression, aligning with immunohistochemistry.
- MUC13-targeted RPT demonstrated in vivo efficacy and improved survival in preclinical models.
Conclusions:
- MUC13-targeted RPT efficacy is linked to radiopharmaceutical accumulation and DNA damage repair gene expression.
- A potential sensitivity signature for MUC13-positive mCRC theranostics was identified.
- Preclinical data support MUC13 as a viable target for mCRC RPT.
