Local control of experimental malignant pancreatic tumors by treatment with a combination of chemotherapy and intratumoral 224Radium-loaded wires releasing alpha-emitting atoms

Galit Horev-Drori, Tomer Cooks, Hadas Bittan, Elinor Lazarov, Michael Schmidt, Lior Arazi, Margalit Efrati, Itzhak Kelson, Yona Keisari*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

We developed 224Ra-loaded wires that when inserted into solid tumors, release radioactive atoms that spread in the tumor and irradiate it effectively with alpha particles (diffusing alpha-emitters radiation therapy [DaRT]). In this study, we tested the ability of intratumoral 224Ra-loaded wires to control the local growth of pancreatic tumors and the enhancement of this effect by chemotherapy. Pancreatic mouse tumors (Panc02) were treated with 224Ra-loaded wire(s) with or without gemcitabine. The tumor size and survival were monitored, and autoradiography was performed to evaluate the spread of radioactive atoms inside the tumor. Mouse and human pancreatic cancer cells, irradiated in vitro by alpha particles with or without chemotherapy, were evaluated for cell growth inhibition. The insertion of 224Ra-loaded wires into pancreatic tumors in combination with gemcitabine achieved significant local control and was superior to each treatment alone. A dosimetric analysis showed the spread of radioactive atoms in the tumor around the wires. Alpha particles combined with gemcitabine or 5-FU killed mouse and human cells in vitro better than each treatment alone. DaRT in combination with gemcitabine was proven effective against pancreatic tumors in vivo and in vitro, and the process may be applicable as a palliative treatment for patients with pancreatic cancer.

Original languageEnglish
Pages (from-to)32-41
Number of pages10
JournalTranslational Research
Volume159
Issue number1
DOIs
StatePublished - Jan 2012

Keywords

  • 5-FU
  • 5-fluorouracil
  • DMEM
  • DSB
  • DaRT
  • Dulbecco's modified eagle medium
  • LET
  • OD
  • PBS
  • SCC
  • SSB
  • diffusing alpha-emitters radiation therapy
  • double strand breaks
  • linear energy transfer
  • optical density
  • phosphate-buffered saline
  • single stranded break
  • squamous cell carcinoma

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