Abstract
We have developed the 16F12 mouse monoclonal antibody (mAb) that targets the MISRII receptor expressed by ovarian tumors. Here, we assessed in preclinical models the possibility to use radiolabeled 16F12 in a theranostic approach for small-volume ovarian peritoneal carcinomatosis, for instance after cytoreductive surgery. Methods: DOTA-, DTPA- or DFO-conjugated 16F12 mAb was radiolabeled with beta (177Lu) or alpha (213Bi) particle emitters for therapeutic use, and with 89Zr for positron emission tomography (PET) imaging. 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 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. Hematological 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. Hematological toxicity was more pronounced with 177Lu-16F12 than 213Bi-16F12. 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 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 of radiolabeled anti-MISRII mAbs a realistic theranostic option for the clinic.
- Oncology: GYN
- Radiobiology/Dosimetry
- Radionuclide Therapy
- MISRII
- Ovarian
- Peritoneal carcinomatosis
- Radioimmunotherapy
- Theranostic
- Copyright © 2018 by the Society of Nuclear Medicine and Molecular Imaging, Inc.