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

被引：16

作者：

Deshayes, Emmanuel ^{[1
,2
]}

Ladjohounlou, Riad ^{[1
]}

Le Fur, Pierre ^{[1
]}

Pichard, Alexandre ^{[1
]}

Lozza, Catherine ^{[1
]}

Boudousq, Vincent ^{[1
]}

Sevestre, Samuel ^{[1
]}

Jarlier, Marta ^{[2
]}

Kashani, Roxana ^{[3
]}

Koch, Joanna ^{[3
]}

Sosabowski, Jane ^{[3
]}

Foster, Julie ^{[3
]}

Chouin, Nicolas ^{[4
,5
]}

Bruchertseifer, Frank ^{[6
]}

Morgenstern, Alfred ^{[6
]}

Kotzki, Pierre-Olivier ^{[1
,2
]}

Navarro-Teulon, Isabelle ^{[1
]}

Pouget, Jean-Pierre ^{[1
]}

机构：

[1] Univ Montpellier, INSERM, Inst Reg Canc Montpellier ICM, IRCM, Montpellier, France

[2] Inst Reg Canc Montpellier, Montpellier, France

[3] Queen Mary Univ London, Barts Canc Inst, Ctr Mol Oncol, London, England

[4] Univ Nantes, Nantes Angers Canc Res Ctr CRCINA, INSERM, CNRS,ERL6001,UMR1232, Nantes, France

[5] Oniris, AMaROC Unit, Nantes, France

[6] European Commiss, Joint Res Ctr, Directorate Nucl Safety & Secur, Karlsruhe, Germany

来源：

JOURNAL OF NUCLEAR MEDICINE | 2018年 / 59卷 / 08期

关键词：

targeted radiotherapy; radioimmunotherapy; theranostic; MISRII; Bi-213; Lu-177; ovarian; peritoneal carcinomatosis; HYPERTHERMIC INTRAPERITONEAL CHEMOTHERAPY; MONOCLONAL-ANTIBODY; ALPHA-RADIOIMMUNOTHERAPY; THERAPEUTIC-EFFICACY; HORMONE; TUMORS; XENOGRAFTS; BINDING; PROTEIN; BETA;

D O I：

10.2967/jnumed.118.208611

中图分类号：

R8 [特种医学]; R445 [影像诊断学];

学科分类号：

1002 ; 100207 ; 1009 ;

摘要：

We have developed the 16F12 mouse monoclonal antibody (mAb), which targets the Mullerian-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 beta-particle (Lu-177) or alpha-particle (Bi-213) emitters for therapeutic use and with Zr-89 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 Lu-177-16F12 or 12.9 MBq of Bi-213-16F12 or by brief intraperitoneal radioimmunotherapy (BIP-RIT) using 50 MBq of Lu-177-16F12 or 37 MBq of Bi-213-16F12. For BIP-RIT, 30 min after injection of the radiolabeled mAbs, the peritoneal cavity was washed to remove the unbound radioactivity. The biodistribution of Lu-177-and Bi-213-16F12 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 Lu-177-16F12 was slightly more efficient in delaying tumor growth than IP-RIT with Bi-213-16F12. Conversely, Bi-213-16F12 was more efficient than Lu-177-16F12 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 Bi-213- and Lu-177-16F12. Hematologic toxicity was more pronounced with Lu-177-16F12 than with Bi-213-16F12. SPECT/CT images (after BIP-RIT with Lu-177-16F12) and PET/CT images (after injection of Zr-89-16F12 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, Bi-213-16F12-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.

引用

页码：1234 / 1242

页数：9

共 47 条

[1]

Andersson H, 2003, CLIN CANCER RES, V9, p3914S

[2] Cure of Human Ovarian Carcinoma Solid Xenografts by Fractionated α-Radioimmunotherapy with 211At-MX35-F(ab')2: Influence of Absorbed Tumor Dose and Effect on Long-Term Survival [J].