Bombesin Encapsulated in Long-Circulating pH-Sensitive Liposomes as a Radiotracer for Breast Tumor Identification

作者：Branco de Barros Andre Luis; Mota Luciene das Gracas; Antunes Coelho Marina Melo; Resende Correa Natassia Caroline; de Goes Alfredo Miranda; Oliveira Monica Cristina; Cardoso Valbert Nascimento

来源：Journal of Biomedical Nanotechnology, 2015, 11(2): 342-350.

DOI：10.1166/jbn.2015.1910

• Bombesin
• Liposomes
• Breast Tumor
• Scintigraphic Imaging
• pH-Sensitivity
• Cryoprotectants

Bombesin (BBN) is a tetradecapeptide that binds specifically to gastrin-releasing peptide receptors in humans. These receptors are over-expressed in several forms of cancer; radiolabeled BBN could therefore be used to detect such cancers. However, the degradation of peptides is a critical issue in the development of tumor tracers. Liposomes can be used to overcome this problem and improve the uptake of tracers by tumors. Therefore, the purpose of this study was to prepare and characterize long-circulating and pH-sensitive liposomes (SpHL) containing Tc-99m-HYNIC-beta Ala-Bombesin((7-14)) (Tc-99m-BBN(7-14)). In addition, the ability of this system to identify human breast cancer tissue was evaluated using biodistribution studies and scintigraphic images. Long-circulating and pH-sensitive liposomes (SpHL) were prepared and freeze-dried in the presence of cryoprotectants (glucose, mannitol, and trehalose). They were subsequently reconstituted with a solution of Tc-99m-HYNIC-beta Ala-Bombesin((7-14)) (Tc-99m-BBN(7-14)). The liposomes were evaluated for size, encapsulation percentage, radiotracer leakage, and storage stability. In addition, in vivo studies were performed in breast tumor-bearing nude mice. Liposomes in the presence of glucose (SpHLG), exhibited a mean diameter of 164.5 +/- 6.5 nm and exhibited a Tc-99m-BBN(7-14) encapsulation percentage of 30%. In addition, they remained highly stable for up to 120 days of storage. SpHLG-Tc-99m-BBN(7-14) showed longer blood circulation than free Tc-99m-BBN(7-14) did. The tumor-to-muscle and tumor-to-blood ratios for SpHLG-Tc-99m-BBN(7-14) were high at 4 h post-injection (9.31%ID/g and 7.93%ID/g, respectively). Furthermore, scintigraphic images revealed a strong signal in the tumor area, indicating tumor specificity of SpHLG-Tc-99m-BBN(7-14). In summary, SpHLG-Tc-99m-BBN(7-14) presented characteristics suitable for a diagnostic agent, and is a potential tool for tumor identification.

• 出版日期2015-2