Theranostic approach in ovarian cancer using Anti-MISRII radiolabeled antibodies

Here, we assessed in preclinical models the possibility to use radiolabeled 16F12, a mouse monoclonal antibody (mAb) that targets the MISRII receptor, in a theranostic approach for small-volume ovarian peritoneal carcinomatosis, for instance after cytoreductive surgery. Methods: The 16F12 mAb was radiolabeled with beta (177Lu) or alpha (213Bi) particle emitters for therapeutic use, and with 89Zr for positron emission tomography (PET) imaging after conjugation with DOTA-, DTPA- or DFO-conjugated, respectively. At day 13 post-xenograft, mice bearing intraperitoneal MISRII-positive AN3CA endometrial carcinoma cell tumor xenografts were treated by conventional intraperitoneal radioimmunotherapy (IP-RIT) with 10 MBq 177Lu-16F12 or 12.9 MBq 213Bi-16F12, or by brief intraperitoneal radioimmunotherapy (BIP-RIT) using 50 MBq 177Lu-16F12 or 37 MBq 213Bi- 16F12. For BIP-RIT, 30 minutes after injection of high activities of radiolabeled mAbs, the peritoneal cavity was washed to remove the unbound radioactivity. The biodistribution of 177Luand 213Bi-16F12 mAbs was determined and then used for dose assessment. Hematological toxicity was also monitored. Results: Tumors were efficiently monitored and SPECT/CT (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 S617 Eur J Nucl Med Mol Imaging (2018) 45 (Suppl 1): S1–S844 site. IP-RIT with 177Lu-16F12 was shown to be 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-toblood uptake ratio was significantly higher with BIP-RIT than with IP-RIT for both 213Bi- and 177Lu-16F12. Hematological toxicity was more pronounced with 177Lu-16F12 than 213Bi-16F12. 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 while 177Lu-16F12 would be more suitable for intravenous RIT. 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.

POUGET Jean-Pierre;  DESHAYES Emmanuel;  LADJOHOUNLOU Riad;  LE FUR Pierre;  PICHARD Alexandre;  LOZZA Catherine;  KASHANI Roxana;  KOCH Joanna;  FOSTER Julie;  SOSABOWSKI Jane;  BRUCHERTSEIFER Frank;  MORGENSTERN Alfred;  CHOUIN N;  NAVARRO-TEULON Isabelle; 

2018-11-12

SPRINGER

JRC113298

1619-7070 (online),   

https://publications.jrc.ec.europa.eu/repository/handle/JRC113298,   

10.1007/s00259-018-4148-3 (online),