Beta emitters rhenium-188 and lutetium-177 are equally effective in radioimmunotherapy of HPV-positive experimental cervical cancer

Rebecca Phaeton, Zewei Jiang, Ekaterina Revskaya, Darrell R. Fisher, Gary L. Goldberg, Ekaterina Dadachova

Research output: Contribution to journalArticle

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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 (188Re) and Lutetium-177 (177Lu)-labeled mAb C1P5 to E6. The biodistribution of 188Re- and 177Lu-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 188Re-C1P5 or 177Lu-C1P5 or left untreated, and observed for their tumor size for 28 days. The levels of 188Re- and 177Lu-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 177Lu-C1P5 and 188Re-C1P5. The dose to the liver was five times higher for 177Lu-C1P5. The doses to the tumor were 259 and 181 cGy for 177Lu-C1P5 and 188Re-C1P5, respectively. RIT with either 177Lu-C1P5 or 188Re-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 177Lu-C1P5 group only and on day 10 it was observed in both 177Lu-C1P5 and 188Re-C1P5 groups. 188Re- and 177Lu-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.

Original languageEnglish (US)
Pages (from-to)9-16
Number of pages8
JournalCancer Medicine
Volume5
Issue number1
DOIs
StatePublished - Jan 1 2016

Fingerprint

Lutetium
Rhenium
Radioimmunotherapy
Uterine Cervical Neoplasms
Neoplasms
Radioisotopes
Monoclonal Antibodies
Staining and Labeling
Radiometry
Oncogene Proteins
Growth
Heterografts
Nude Mice
Clinical Trials
Radiation
Lung
Antibodies
Liver

Keywords

  • Cervical cancer
  • E6 and E7 oncogenes
  • Luthetium-177
  • Radioimmunotherapy
  • Rhenium-188

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Cite this

Beta emitters rhenium-188 and lutetium-177 are equally effective in radioimmunotherapy of HPV-positive experimental cervical cancer. / Phaeton, Rebecca; Jiang, Zewei; Revskaya, Ekaterina; Fisher, Darrell R.; Goldberg, Gary L.; Dadachova, Ekaterina.

In: Cancer Medicine, Vol. 5, No. 1, 01.01.2016, p. 9-16.

Research output: Contribution to journalArticle

Phaeton, Rebecca ; Jiang, Zewei ; Revskaya, Ekaterina ; Fisher, Darrell R. ; Goldberg, Gary L. ; Dadachova, Ekaterina. / Beta emitters rhenium-188 and lutetium-177 are equally effective in radioimmunotherapy of HPV-positive experimental cervical cancer. In: Cancer Medicine. 2016 ; Vol. 5, No. 1. pp. 9-16.
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