Development and Testing of (212)Pb/(212)Bi Peptide for Targeting Metastatic Melanoma.

摘要

Metastatic melanoma (common skin cancer) develops from malignant transformation of the melanocyte, a cell that produces the pigment melanin. Melanomas spread superficially or systemically by nodular invasion. Metastases spread to regional lymph nodes and then distally to the lungs, liver, bone, and brain, where they grow into large tumor masses. Melanoma, a cell type that is highly radiation-resistant, is treated by wide surgical excision of primary tumors. However, distal symptomatic metastases can only be treated by chemotherapy (dicarbazine, temozolomide, paclitaxel, or cisplatin), which produce low response rates to therapy (15%), serious side-effects, and no improvement in overall survival. Current medical treatments are rarely successful, and the prognosis for patients diagnosed with metastatic melanoma is poor (Claveau et al., 2009). The need for improved and more effective therapies against metastatic melanoma is well-confirmed by recent clinical studies. Radiation biologists recognize that alpha particles are effective in killing melanoma cancer cells. High-linear-energy alpha particles can be effective in treating radiation-resistant disease that responds poorly to traditional low-linear-energy beta/gamma emitters (Sgouros et al., 2010). Because of the short range of alpha particles (40 to 70 micrometers in soft tissue), and to be effective in cell killing, the alpha-emitters need to be delivered directly to cancer cells using cell-targeted radioimmunotherapy.