title: Beta emitters rhenium-188 and lutetium-177 are equally effective in radioimmunotherapy of HPV-positive experimental cervical cancer.
abstract: Cervical cancer caused by the infection with the human papillomavirus (HPV) remains the fourth leading killer of women worldwide. Therefore, more efficacious treatments are needed. We are developing radioimmunotherapy (RIT) of HPV-positive cervical cancers by targeting E6 and E7 viral oncoproteins expressed by the cancer cells with the radiolabeled monoclonal antibodies (mAbs). To investigate the influence of different radionuclides on the RIT efficacy-we performed RIT of experimental cervical cancer with Rhenium-188 ((188) Re) and Lutetium-177 ((177) Lu)-labeled mAb C1P5 to E6. The biodistribution of (188) Re- and (177) Lu-labeled C1P5 was performed in nude female mice bearing CasKi cervical cancer xenografts and the radiation dosimetry calculations for the tumors and organs were carried out. For RIT the mice were treated with 7.4 MBq of either (188) Re-C1P5 or (177) Lu-C1P5 or left untreated, and observed for their tumor size for 28 days. The levels of (188) Re- and (177) Lu-C1P5 mAbs-induced double-strand breaks in CasKi tumors were compared on days 5 and 10 post treatment by staining with anti-gamma H2AX antibody. The radiation doses to the heart and lungs were similar for both (177) Lu-C1P5 and (188) Re-C1P5. The dose to the liver was five times higher for (177) Lu-C1P5. The doses to the tumor were 259 and 181 cGy for (177) Lu-C1P5 and (188) Re-C1P5, respectively. RIT with either (177) Lu-C1P5 or (188) Re-C1P5 was equally effective in inhibiting tumor growth when each was compared to the untreated controls (P = 0.001). On day 5 there was a pronounced staining for gamma H2AX foci in (177) Lu-C1P5 group only and on day 10 it was observed in both (177) Lu-C1P5 and (188) Re-C1P5 groups. (188) Re- and (177) Lu-labeled mAbs were equally effective in arresting the growth of CasKi cervical tumors. Thus, both of these radionuclides are candidates for the clinical trials of this approach in patients with advanced, recurrent or metastatic cervical cancer.
authors.affiliation: Department of Obstetrics and Gynecology, Penn State Hershey Medical Center, Hershey, Pennsylvania.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Phaeton
authors.affiliation: Department of Radiology, Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Zewei
authors.initials: Z
authors.lastname: Jiang
authors.affiliation: Department of Radiology, Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Revskaya
authors.affiliation: Dade Moeller Health System, Richland, Washington.
authors.forename: Darrell R
authors.initials: DR
authors.lastname: Fisher
authors.affiliation: Department of Obstetrics and Gynecology, Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Gary L
authors.initials: GL
authors.lastname: Goldberg
authors.affiliation: Department of Radiology, Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Dadachova
mesh_terms: D000818:Animals; D001610:Beta Particles; D045744:Cell Line, Tumor; D004249:DNA Damage / Q000528:radiation effects; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D018796:Immunoconjugates / Q000494:pharmacology* / Q000627:therapeutic use; D008187:Lutetium / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D030361:Papillomavirus Infections / Q000150:complications / Q000821:virology; D016499:Radioimmunotherapy; D011868:Radioisotopes / Q000494:pharmacology* / Q000627:therapeutic use; D012211:Rhenium / Q000494:pharmacology* / Q000627:therapeutic use; D014018:Tissue Distribution; D002583:Uterine Cervical Neoplasms / Q000209:etiology* / Q000473:pathology* / Q000532:radiotherapy; D023041:Xenograft Model Antitumor Assays
chemical_list: D018796:Immunoconjugates; D011868:Radioisotopes; D008187:Lutetium; D012211:Rhenium
keywords: Cervical cancer; E6 and E7 oncogenes; luthetium-177; radioimmunotherapy; rhenium-188