HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

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

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.
AuthorsEmmanuel Deshayes, Riad Ladjohounlou, Pierre Le Fur, Alexandre Pichard, Catherine Lozza, Vincent Boudousq, Samuel Sevestre, Marta Jarlier, Roxana Kashani, Joanna Koch, Jane Sosabowski, Julie Foster, Nicolas Chouin, Frank Bruchertseifer, Alfred Morgenstern, Pierre-Olivier Kotzki, Isabelle Navarro-Teulon, Jean-Pierre Pouget
JournalJournal of nuclear medicine : official publication, Society of Nuclear Medicine (J Nucl Med) Vol. 59 Issue 8 Pg. 1234-1242 (08 2018) ISSN: 1535-5667 [Electronic] United States
PMID29674421 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright© 2018 by the Society of Nuclear Medicine and Molecular Imaging.
Chemical References
  • Antibodies, Monoclonal
  • Heterocyclic Compounds, 1-Ring
  • Receptors, Peptide
  • Receptors, Transforming Growth Factor beta
  • anti-Mullerian hormone receptor
  • 1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid
  • Pentetic Acid
  • Deferoxamine
Topics
  • Animals
  • Antibodies, Monoclonal (chemistry, pharmacokinetics, therapeutic use)
  • Cell Line, Tumor
  • Deferoxamine (chemistry)
  • Female
  • Heterocyclic Compounds, 1-Ring (chemistry)
  • Humans
  • Isotope Labeling
  • Mice
  • Ovarian Neoplasms (diagnostic imaging, metabolism, radiotherapy)
  • Pentetic Acid (chemistry)
  • Positron Emission Tomography Computed Tomography
  • Radiochemistry
  • Receptors, Peptide (immunology)
  • Receptors, Transforming Growth Factor beta (immunology)
  • Tissue Distribution

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: