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

摘要

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.