Tc-labeled bombesin analog for breast cancer identification

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-β[Ala-Bombesin.sub.(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. [sup.99m]Tc-HYNIC- β[Ala-Bombesin.sub.(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 [sup.99m]Tc-HYNIC-β[Ala-Bombesin.sub.(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 [sup.99m]Tc-HYNIC-β[Ala-Bombesin.sub.(7-14)]. The [sup.99m]Tc-HYNIC-β[Ala-Bombesin.sub.(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. Keywords Bombesin * MDA-MB-231 * Breast tumor * Scintigraphic imaging * Diagnosis * Radiolabeled peptide