99mTc-labeled bombesin analog for breast cancer identification

• Published in: Journal of radioanalytical and nuclear chemistry Vol. 295; no. 3; pp. 2083 - 2090
• Main Authors: de Barros, André Luís Branco, das Graças Mota, Luciene, de Aguiar Ferreira, Carolina, Corrêa, Natássia Caroline Resende, de Góes, Alfredo Miranda, Oliveira, Mônica Cristina, Cardoso, Valbert Nascimento
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01-03-2013
• Subjects: Affinity; Biotechnology; Breast; Cancer; Chemistry; Chemistry and Materials Science; Diagnostic Radiology; Hadrons; Heavy Ions; In vitro testing; Inorganic Chemistry; Nuclear Chemistry; Nuclear Physics; Peptides; Physical Chemistry; Receptors; Tumors; Scintigraphic imaging; Radiolabeled peptide; Bombesin; Diagnosis; Breast tumor; MDA-MB-231
• ISSN: 0236-5731; 1588-2780
• DOI: 10.1007/s10967-012-2331-8

Bombesin is a tetradecapeptide that binds specifically to gastrin releasing peptide receptors in humans. Several forms of cancer, including lung, prostate, breast, and colon express receptors for bombesin-like peptides. Radiolabeled bombesin analogs with a high affinity for these receptors might therefore be used for scintigraphic imaging of these tumor types. A truncated bombesin derivative (HYNIC-βAla-Bombesin
(7–14)
) was radiolabeled with technetium-99m using EDDA and tricine as coligands. In vitro stability was evaluated in presence of plasma and excess of cysteine. The receptor-binding affinity assays was evaluated in MDA-MB-231 cancer cell line. In addition, in vivo biodistribution was performed in nude mice bearing breast tumor. In vitro assay showed a good affinity for the MDA-MB-231 cell line, showing 20.0 % of internalization at 4 h post-administration.
99m
Tc-HYNIC-βAla-Bombesin
(7–14)
biodistribution revealed a rapid clearance and a significant renal excretion. In addition, tumor uptake was higher than non-excretory organs, such as the spleen, the liver, and muscles. Tumor-to-muscle and tumor-to-blood ratios for
99m
Tc-HYNIC-βAla-Bombesin
(7–14)
showed high values at 4 h post-injection (5.34 and 4.55, respectively). Furthermore, blocked studies using cold bombesin peptide were performed, which demonstrated an important decrease in tumor uptake, indicating a tumor specificity for
99m
Tc-HYNIC-βAla-Bombesin
(7–14)
. The
99m
Tc-HYNIC-βAla-Bombesin
(7–14)
displayed suitable radiochemical characteristics, and adequate affinity to breast tumor cells (MDA-MB-231). Therefore, this analog can be considered as a candidate for the identification of bombesin-positive tumors.