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Updated: Feb 11, 2026
An Orthotopic Model of Serous Ovarian Cancer in Immunocompetent Mice for in vivo Tumor Imaging and Monitoring of Tumor Immune Responses
Published on: November 28, 2010
Radiolabeled Antibodies Against Müllerian-Inhibiting Substance Receptor, Type II: New Tools for a Theranostic
Emmanuel Deshayes1,2, Riad Ladjohounlou1, Pierre Le Fur1
1Institut de Recherche en Cancérologie de Montpellier (IRCM), INSERM, Université de Montpellier, Institut Régional du Cancer de Montpellier (ICM), Montpellier, France.
Abstract:
We have developed the 16F12 mouse monoclonal antibody (mAb), which targets the Müllerian-inhibiting substance receptor, type II (MISRII), expressed by ovarian tumors. Here, we assessed in preclinical models the possibility of using radiolabeled 16F12 in a theranostic approach for small-volume ovarian peritoneal carcinomatosis, such as after cytoreductive surgery. Methods: DOTA-, DTPA- or deferoxamine mesylate-conjugated 16F12 mAb was radiolabeled with β-particle (177Lu) or α-particle (213Bi) emitters for therapeutic use and with 89Zr for PET imaging. On the 13th postxenograft day, mice bearing intraperitoneal MISRII-positive AN3CA endometrial carcinoma cell xenografts were treated by conventional intraperitoneal radioimmunotherapy (IP-RIT) with 10 MBq of 177Lu-16F12 or 12.9 MBq of 213Bi-16F12 or by brief intraperitoneal radioimmunotherapy (BIP-RIT) using 50 MBq of 177Lu-16F12 or 37 MBq of 213Bi-16F12. For BIP-RIT, 30 min after injection of the radiolabeled mAbs, the peritoneal cavity was washed to remove the unbound radioactivity. The biodistribution of 177Lu- and 213Bi-16F12 mAbs was determined and then used for dose assessment. Hematologic toxicity was also monitored. Results: The 16F12 mAb was satisfactorily radiolabeled for both therapy and imaging. IP-RIT with 177Lu-16F12 was slightly more efficient in delaying tumor growth than IP-RIT with 213Bi-16F12. Conversely, 213Bi-16F12 was more efficient than 177Lu-16F12 in BIP-RIT. The biodistribution analysis showed that the tumor-to-blood uptake ratio was significantly higher with BIP-RIT than with IP-RIT for both 213Bi- and 177Lu-16F12. Hematologic toxicity was more pronounced with 177Lu-16F12 than with 213Bi-16F12. SPECT/CT images (after BIP-RIT with 177Lu-16F12) and PET/CT images (after injection of 89Zr-16F12 in the tail vein) showed focal uptake at the tumor site. Conclusion: Radiolabeled 16F12 could represent a new theranostic tool for small-volume ovarian peritoneal carcinomatosis. Specifically, 213Bi-16F12-based BIP-RIT could be proposed to selected patients as an alternative adjuvant treatment immediately after cytoreductive surgery. An anti-MISRII mAb is currently being used in a first-in-human study, thus making radiolabeled anti-MISRII mAbs a realistic theranostic option for the clinic.
Insights
Radiolabeled 16F12 antibody shows promise as a theranostic tool for ovarian cancer. Brief intraperitoneal radioimmunotherapy (BIP-RIT) using Bismuth-213-labeled 16F12 (213Bi-16F12) demonstrated superior tumor targeting and reduced toxicity in preclinical models.
Area of Science:
- Oncology
- Radiopharmaceutical Therapy
- Molecular Imaging
Background:
- Ovarian peritoneal carcinomatosis is a significant challenge in gynecologic oncology.
- The Müllerian-inhibiting substance receptor, type II (MISRII) is expressed on ovarian tumors, presenting a potential therapeutic target.
- Theranostic approaches combining diagnosis and therapy offer personalized treatment strategies.
Purpose of the Study:
- To evaluate the theranostic potential of radiolabeled 16F12 monoclonal antibody (mAb) in preclinical models of ovarian cancer.
- To compare the efficacy and toxicity of different radioimmunotherapy (RIT) methods using Lutetium-177 (177Lu) and Bismuth-213 (213Bi) labeled 16F12.
- To assess the utility of radiolabeled 16F12 for imaging ovarian peritoneal carcinomatosis.
Main Methods:
- 16F12 mAb was conjugated and radiolabeled with 177Lu, 213Bi, or Zirconium-89 (89Zr).
- Preclinical models with intraperitoneal MISRII-positive tumors were treated with conventional intraperitoneal RIT (IP-RIT) or brief intraperitoneal RIT (BIP-RIT).
- Biodistribution, tumor uptake, and hematologic toxicity were evaluated; imaging was performed using SPECT/CT and PET/CT.
Main Results:
- Radiolabeling of 16F12 was successful for both therapeutic and imaging applications.
- BIP-RIT with 213Bi-16F12 showed higher tumor-to-blood uptake ratios and greater efficiency than IP-RIT.
- SPECT/CT and PET/CT imaging demonstrated focal uptake at tumor sites, confirming targeting accuracy.
Conclusions:
- Radiolabeled 16F12 represents a promising theranostic agent for small-volume ovarian peritoneal carcinomatosis.
- 213Bi-16F12-based BIP-RIT is a potential adjuvant treatment option post-cytoreductive surgery for selected patients.
- The development of anti-MISRII mAbs for theranostic use is advancing towards clinical application.
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