Imaging the Distribution of Gastrin-Releasing Peptide Receptors in Cancer

Abstract

Targeting tumor-expressed receptors using selective molecules for diagnostic, therapeutic, or both diagnostic and therapeutic (theragnostic) purposes is a promising approach in oncologic applications. Such approaches have increased significantly over the past decade. Peptides such as gastrin-releasing peptide receptors targeting radiopharmaceuticals are small molecules with fast blood clearance and urinary excretion. They demonstrate good tissue diffusion, low immunogenicity, and highly selective binding to their target cell-surface receptors. They are also easily produced. Gastrin-releasing peptide receptors, part of the bombesin family, are overexpressed in many tumors, including breast and prostate cancer, and therefore represent an attractive target for future development.

Gastrin releasing peptide receptor targeted nano-graphene oxide for near-infrared fluorescence imaging of oral squamous cell carcinoma

“…AF750-6Ahx-Sta-BBN is a GRPR antagonist peptide analog. Siyuan Cheng et al 34 compared GRPR agonist BBN (7)(8)(9)(10)(11)(12)(13)(14) and GRPR antagonist RM26 for prostate cancer PET imaging and found that GRPR antagonist is a candidate for clinical transformation. This present study is the first study to demonstrate the potential of using a GRPR antagonist AF750-6Ahx-Sta-BBN as a potential near-infrared fluorescence imaging probe for OSCC detection.…”

“…NaHCO 3 , DMF and other regular reagents were purchased from Sigma-Aldrich (St. Louis, MO, USA). Full length bombesin [1][2][3][4][5][6][7][8][9][10][11][12][13][14] from American Peptide Company (Sunnyvale, CA, USA) was used as the blocking agent in this study. AF750- www.nature.com/scientificreports/ 6Ahx-Sta-BBN was synthesized and purified at the Biomolecular Imaging Center, Harry S. Truman Memorial Veterans' Hospital, and University of Missouri, Columbia, Missouri, United States, according to our published procedure 27 .…”

“…In vitro quantification of binding affinity to GRPR was performed with the effective concentration 50 percent (EC50) assay. Briefly, a series of samples each with 1 × 10 6 HSC-3 human OSCC cells in culture medium were incubated with 1.5 nM BBN (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14), and added with increasing concentrations (5 × 10 -3 nM to 5 × 10 1 nM) of AF750-6Ahx-Sta-BBN or NGO-BBN-AF750 at 37 °C and 5% CO 2 for 50 min. The incubation medium was subsequently aspirated, and the cells were washed three times with ice cold media.…”

“…The result indicates that AF750-6Ahx-Sta-BBN specifically binds to the GRPR on HSC-3 cells. To determine the binding affinity of AF750-6Ahx-Sta-BBN in HSC-3, cells were first incubated with BBN (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14), then added increasing concentrations of AF750-6Ahx-Sta-BBN (0.005-50 nM). Cells were washed after 50 min incubation and examined by flow cytometry.…”

“…www.nature.com/scientificreports/ researchers have also shown that other tumors overexpress GRPR on their cell surface, including head/neck 14 . GRPR was further used as a biomarker for surgical margin prediction in a murine orthotopic model of oral cancer and a strong expression of GRPR was observed uniformly in primary OSCC sections as compared to respective adjacent non-malignant region 15 .…”