title: Local control of experimental malignant pancreatic tumors by treatment with a combination of chemotherapy and intratumoral 224radium-loaded wires releasing alpha-emitting atoms.
abstract: We developed (224)Ra-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 (224)Ra-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 (224)Ra-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 (224)Ra-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.
authors.affiliation: Department of Clinical Microbiology and Immunology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Galit
authors.initials: G
authors.lastname: Horev-Drori
authors.forename: Tomer
authors.initials: T
authors.lastname: Cooks
authors.forename: Hadas
authors.initials: H
authors.lastname: Bittan
authors.forename: Elinor
authors.initials: E
authors.lastname: Lazarov
authors.forename: Michael
authors.initials: M
authors.lastname: Schmidt
authors.forename: Lior
authors.initials: L
authors.lastname: Arazi
authors.forename: Margalit
authors.initials: M
authors.lastname: Efrati
authors.forename: Itzhak
authors.initials: I
authors.lastname: Kelson
authors.forename: Yona
authors.initials: Y
authors.lastname: Keisari
mesh_terms: D000512:Alpha Particles / Q000627:therapeutic use; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D001918:Brachytherapy / Q000379:methods; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D059248:Chemoradiotherapy; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D004195:Disease Models, Animal; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D010179:Pancreas / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000532:radiotherapy; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D011883:Radium / Q000627:therapeutic use*; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D011838:Radiation-Sensitizing Agents; D003841:Deoxycytidine; D005472:Fluorouracil; D011883:Radium; D000093542:Gemcitabine