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.