Bombesin Encapsulated in Long-Circulating pH-Sensitive Liposomes as a Radiotracer for Breast Tumor Identification.
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 99mTc-HYNIC-βAla-Bombesin(7-14) (99mTc-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 99mTc-HYNIC-βAla-Bombesin(7-14) (99mTc-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 99mTc-BBN(7-14) encapsulation percentage of 30%. In addition, they remained highly stable for up to 120 days of storage. SpHLG- 99mTc-BBN(7-14) showed longer blood circulation than free 99mTc-BBN(7-14), did. The tumor-to-muscle and tumor-to-blood ratios for SpHLG-99mTc-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-99mTc-BBN(7-14). In summary, SpHLG-99mTc-BBN(7-14) presented characteristics suitable for a diagnostic agent, and is a potential tool for tumor identification.
André Luís Branco
AL
De Barros
Luciene Das Graças
LD
Mota
Marina Melo Antunes
MM
Coelho
Natássia Caroline Resende
NC
Corrêa
Alfredo Miranda
AM
De Góes
Mônica Cristina
MC
Oliveira
Valbert Nascimento
VN
Cardoso
D000818:Animals; D001839:Bombesin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism; D004339:Drug Compounding; D005260:Female; D006801:Humans; D006834:Hydrazines / Q000737:chemistry / Q000493:pharmacokinetics; D006863:Hydrogen-Ion Concentration; D008081:Liposomes / Q000737:chemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009539:Nicotinic Acids / Q000737:chemistry / Q000493:pharmacokinetics; D015609:Organotechnetium Compounds; D010446:Peptide Fragments / Q000737:chemistry / Q000493:pharmacokinetics; D011849:Radioactive Tracers; D011877:Radionuclide Imaging; D014407:Tumor Cells, Cultured
C120392:6-hydrazinopyridine-3-carboxylic acid; D006834:Hydrazines; D008081:Liposomes; D009539:Nicotinic Acids; D015609:Organotechnetium Compounds; D010446:Peptide Fragments; D011849:Radioactive Tracers; C118536:bombesin (7-14); D001839:Bombesin