A fast tumor‐targeting near‐infrared fluorescent probe based on bombesin analog for in vivo tumor imaging

Abstract

Bombesin (BBN), an analog of gastrin-releasing peptide (GRP), of which the receptors are over-expressed on various tumor cells, is able to bind to GRP receptor specifically. In this study, a near-infrared fluorescent dye (MPA) and polyethylene glycol (PEG) were conjugated to BBN analog to form BBN[7-14]-MPA and BBN[7-14]-SA-PEG-MPA. The successful synthesis of the two probes was proved by the characterization via sodium dodecylsulfate-polyacrylamide gel electrophoresis, infrared and optical spectra. Cellular uptakes studies indicated that BBN-based probes were mediated by gastrin-releasing peptide receptors (GRPR) on tumor cells and the PEG modified probe had higher affinity. The dynamic distribution and clearance investigations showed that the BBN-based probes were eliminated by the liver-kidney pathway. Furthermore, both of the BBN-based probes displayed tumor-targeting ability in GRPR over-expressed tumor-bearing mice. The PEG modified probe exhibited faster and higher tumor targeting capability than BBN[7-14]-MPA. The results implied that BBN[7-14]-SA-PEG-MPA could act as an effective fluorescence probe for tumor imaging.

Gastrin-Releasing Peptide Receptor- and Prostate-Specific Membrane Antigen-Specific Ultrasmall Gold Nanoparticles for Characterization and Diagnosis of Prostate Carcinoma via Fluorescence Imaging

“…The injected amount of AuNP 4 and 7 corresponded to 1.5 μg (1.75 nmol) of fluorescent dye (AuNP 4 and 7 contain 2% dye; see SI Table S-1). This amount is comparable to literature values lying between 1 and 50 μg/g ,− for dye-BBN conjugates for in vivo fluorescence imaging of tumors. Six mice received AuNP 7 , three mice received AuNP 7 plus coinjection of BBN (7–14) ( c = 1 μg/g), four mice received peptide 15 , and five mice received AuNP 4 .…”

Hybrid Multimodal Imaging Synthons for Chemoselective and Efficient Biomolecule Modification with Chelator and Near-Infrared Fluorescent Cyanine Dye

“…Radiolabeled GRPR-specific peptides have been the focus of radiochemical research for many years as this receptor type is highly overexpressed on a variety of tumors [ 4 ]. However, only one multimodal bombesin (BBN) analog has been reported for combined optical and photoacoustic imaging so far [ 22 ]. For GRPR-targeting, it was shown before that homodimers of GRPR-specific peptides enable an increased target affinity and tumor visualization sensitivity and thus exhibit superior properties compared to their monovalent counterparts [ 23 , 24 ].…”

Bombesin related peptides/receptors and their promising therapeutic roles in cancer imaging, targeting and treatment

“…These include: coupling to fluorescent-probes to be used for optical-imaging[66–68]; coupling to gold-nanorods coated with PEG which can be used for photoacoustical imaging for use particularly in breast-cancers idenfication[69]; conjugation to superparamagnetic iron oxide nanoparticles[70,71] or to other contrast agents[Gd-TTDA-NP, a protein based contrast agent, ProCA1] enhances detection by MRI; magnetofluorescent polymeric nanoparticles coupled to BnR-agonists improve the localization of the nanoparticles in PC-3 bearing mice compared to nanoparticles without coupling to a Bn-agonist, suggesting this approach could be useful for prostate-cancer imaging[72]; and the use of radiolabeled-monoclonal antibodies to proGRP to image tumors(gastric, lung) overexpressing Bn-related peptides.…”