Interstitial wires releasing diffusing alpha emitters combined with chemotherapy improved local tumor control and survival in squamous cell carcinoma-bearing mice

Tomer Cooks, Lior Arazi, Margalit Efrati, Michael Schmidt, Gideon Marshak, Itzhak Kelson, Yona Keisari

Research output: Contribution to journalArticlepeer-review

Abstract

Background: The objective of this study was to examine the combined effect of diffusing alpha-emitter radiation therapy (DART) together with the chemotherapeutic agent cisplatin on tumor development. Methods: BALB/c mice bearing squamous cell carcinoma tumors were treated with radium 224 ( 224Ra-)- loaded stainless steel wires, releasing short-lived, alpha-emitting atoms from their surface. A concomitant regimen of cisplatin doses (5 mg/kg per dose) was given intravenously for the evaluation of the combined effect. Animals were monitored for tumor growth and survival. Results: First, the authors observed that alpha particles and cisplatin inhibited SQ2 cell proliferation in vitro and promoted apoptosis. Treatment of tumor-bearing mice indicated that, when a regimen of 2 separate doses of cisplatin was given concomi- tantly with a single intratumoral 224Ra-loaded wire, there was moderate tumor growth inhibition relative to what was observed from each treatment alone. When tumors were treated with 2 radioactive wires positioned near the tumor base and a similar drug administration, the growth arrest effect intensified, and there also was a significant increase in survival rates. The combined treatment reduced both local tumor growth and metastatic spread to the lungs. Conclusions: Antitumor activity and overall survival of metastatic tumor-bearing mice were improved significantly by the combined treatment. These results highlight the potential benefit of alpha radiation-based radiotherapy in combination with chemotherapeutic drugs for anticancer treatment.

Original languageEnglish
Pages (from-to)1791-1801
Number of pages11
JournalCancer
Volume115
Issue number8
DOIs
StatePublished - 15 Apr 2009

Keywords

  • Alpha radiation
  • Chemoradiotherapy
  • Cisplatin
  • Squamous cell carcinoma

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