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J Nucl Med. 2018 Aug;59(8):1234-1242. doi: 10.2967/jnumed.118.208611. Epub 2018 Apr 19.

Radiolabeled Antibodies Against Müllerian-Inhibiting Substance Receptor, Type II: New Tools for a Theranostic Approach in Ovarian Cancer.

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Institut de Recherche en Cancérologie de Montpellier (IRCM), INSERM, Université de Montpellier, Institut Régional du Cancer de Montpellier (ICM), Montpellier, France.
Institut régional du Cancer de Montpellier, Montpellier, France.
Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom.
Nantes-Angers Cancer Research Center CRCINA, University of Nantes, INSERM UMR1232, CNRS-ERL6001, Nantes, France.
Oniris, AMaROC Unit, Nantes, France; and.
Directorate for Nuclear Safety and Security, Joint Research Centre, European Commission, Karlsruhe, Germany.
Institut de Recherche en Cancérologie de Montpellier (IRCM), INSERM, Université de Montpellier, Institut Régional du Cancer de Montpellier (ICM), Montpellier, France


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.


177Lu; 213Bi; MISRII; ovarian; peritoneal carcinomatosis; radioimmunotherapy; targeted radiotherapy; theranostic


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