Growth retardation and destruction of experimental squamous cell carcinoma by interstitial radioactive wires releasing diffusing alpha-emitting atoms


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Abstract

In the present study, we examined the antitumoral effects caused by the release of alpha emitting radioisotopes into solid squamous cell carcinoma (SCC) tumors. Using a novel method termed DART (Diffusing Alpha-emitters Radiation Therapy), we assessed the efficacy of short-lived daughters of 224Ra releasing alpha particles, dispersing in the malignant tissue, to cause tumor growth retardation and destruction. It was carried out using specially designed wires loaded with 224Ra activities in the range of 7–42 kBq in a set of experiments performed on BALB/c and nude mice bearing metastatic SCC tumors derived from either mouse SQ2 or human CAL27 cell lines. The insertion of a DART wire to the center of 6–7 mm primary tumors, retarded tumor growth, reduced lung metastatic load, prolonged life expectancy and in some cases caused tumor eradication. These effects were enhanced either when treating smaller tumors or treating identical tumors with 2 DART wires. Similar experiments on human-derived SCC tumors in nude mice were consistent with the outcomes of the murine model. Histological assessments revealed the tissue damage pattern, and indicated a role for the tumor vasculature in the dispersion of the atoms and the propagation of the damage. Our findings indicate that Diffusing Alpha-emitting Radiation Therapy is effective in a model system using SCC primary tumors. Thein situdestruction of primary solid tumors by DART is evidently a necessary step toward curing cancer and might be augmented by chemotherapy and other modalities such as immunotherapy or antigrowth factors agents.

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