External beam radiotherapy synergizes ¹⁸⁸Re-liposome against human esophageal cancer xenograft and modulates ¹⁸⁸Re-liposome pharmacokinetics

Abstract

External beam radiotherapy (EBRT) treats gross tumors and local microscopic diseases. Radionuclide therapy by radioisotopes can eradicate tumors systemically. Rhenium 188 (¹⁸⁸Re)-liposome, a nanoparticle undergoing clinical trials, emits gamma rays for imaging validation and beta rays for therapy, with biodistribution profiles preferential to tumors. We designed a combinatory treatment and examined its effects on human esophageal cancer xenografts, a malignancy with potential treatment resistance and poor prognosis. Human esophageal cancer cell lines BE-3 (adenocarcinoma) and CE81T/VGH (squamous cell carcinoma) were implanted and compared. The radiochemical purity of ¹⁸⁸Re-liposome exceeded 95%. Molecular imaging by NanoSPECT/CT showed that BE-3, but not CE81T/VGH, xenografts could uptake the ¹⁸⁸Re-liposome. The combination of EBRT and ¹⁸⁸Re-liposome inhibited tumor regrowth greater than each treatment alone, as the tumor growth inhibition rate was 30% with EBRT, 25% with ¹⁸⁸Re-liposome, and 53% with the combination treatment at 21 days postinjection. Combinatory treatment had no additive adverse effects and significant biological toxicities on white blood cell counts, body weight, or liver and renal functions. EBRT significantly enhanced the excretion of ¹⁸⁸Re-liposome into feces and urine. In conclusion, the combination of EBRT with ¹⁸⁸Re-liposome might be a potential treatment modality for esophageal cancer.

Keywords:

• Radionuclide therapy
• liposome
• teletherapy
• biodistribution

Acknowledgments

This study was supported by grants NSC 100-2623-E-195-NU, 101-2623-E-195-NU and 102-2623-E-195-NU from the National Science Council, Taiwan, and grant MMH-E-102-13 from Mackay Memorial Hospital, Taipei, Taiwan. We presented an earlier version of the abstract in a poster at the 23rd Biennial Congress of the European Association for Cancer Research in Munich (Germany) in 2014.

Disclosure

The authors report no conflicts of interest in this work.