thorium-x and Lung-Neoplasms

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.. BALB/c mice bearing squamous cell carcinoma tumors were treated with radium 224 ((224)Ra-)-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.. 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 concomitantly with a single intratumoral (224)Ra-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.. 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.

Topics: Alpha Particles; Animals; Apoptosis; Brachytherapy; Carcinoma, Squamous Cell; Cell Line, Tumor; Cisplatin; Combined Modality Therapy; Dose-Response Relationship, Radiation; Lung Neoplasms; Male; Mice; Mice, Inbred BALB C; Radium; Survival Rate; Thorium; Xenograft Model Antitumor Assays

Diffusing alpha-emitters radiation therapy (DART) is a new form of brachytherapy enabling the treatment of solid tumors with alpha radiation. The present study examines the antitumoral effects resulting from the release of alpha emitting radioisotopes into solid lung carcinoma (LL2, A427, and NCI-H520).. An in vitro setup tested the dose-dependent killing of tumor cells exposed to alpha particles. In in vivo studies, radioactive wires (0.3 mm diameter, 5 mm long) with (224)Ra activities in the range of 21-38 kBq were inserted into LL/2 tumors in C57BL/6 mice and into human-derived A427 or NCI-H520 tumors in athymic mice. The efficacy of the short-lived daughters of (224)Ra to produce tumor growth retardation and prolong life was assessed, and the spread of radioisotopes inside tumors was measured using autoradiography.. The insertion of a single DART wire into the center of 6- to 7-mm tumors had a pronounced retardation effect on tumor growth, leading to a significant inhibition of 49% (LL2) and 93% (A427) in tumor development and prolongations of 48% (LL2) in life expectancy. In the human model, more than 80% of the treated tumors disappeared or shrunk. Autoradiographic analysis of the treated sectioned tissue revealed the intratumoral distribution of the radioisotopes, and histological analysis showed corresponding areas of necrosis. In vitro experiments demonstrated a dose-dependent killing of tumors cells exposed to alpha particles.. Short-lived diffusing alpha-emitters produced tumor growth retardation and increased survival in mice bearing lung tumor implants. These results justify further investigations with improved dose distributions.

Topics: Alpha Particles; Animals; Autoradiography; Brachytherapy; Dose-Response Relationship, Radiation; Humans; Lead Radioisotopes; Lung Neoplasms; Male; Mice; Mice, Inbred C57BL; Mice, Nude; Neoplastic Stem Cells; Radiotherapy Dosage; Radium; Thorium