Lutetium-177 Labeled Bombesin Peptides for Radionuclide Therapy

Title:Lutetium-177 Labeled Bombesin Peptides for Radionuclide Therapy

Volume: 9 Issue: 1

Author(s): Tamila Stott Reynolds, Rajendra P. Bandari, Zongrun Jiang and Charles J. Smith

Affiliation:

Keywords: Bombesin, cancer, gastrin-releasing peptide, lutetium-177.

Abstract: The rare-earth radionuclides that decay by beta particle (β^-) emission are considered to be ideal in the context of targeted radiotherapy. The rare-earth isotopes exist primarily in the 3+ oxidation state and are considered to be hard metal centers, requiring multidentate, hard donor ligands such as the poly(aminocarboxylates) for in vivo kinetic inertness. ¹⁷⁷Lu is a rare-earth radionuclide that is produced in moderate specific activity (740 GBq/mg) by direct neutron capture of enriched 176Lu via the ¹⁷⁶Lu(n,γ)¹⁷⁷Lu nuclear reaction. ¹⁷⁷Lu has a half-life of 6.71 d, decays by beta emission (E_bmax = 0.497 MeV), and emits two imagable photons (113keV, 3% and 208kev, 11%). High specific activity, no-carrier-added ¹⁷⁷Lu can also be prepared by an indirect neutron capture nuclear reaction on a ¹⁷⁶Yb target.

Herein, we report upon bombesin (BBN) peptides radiolabeled with ¹⁷⁷Lu. The impetus driving many of the research studies that we have described in this review is that the high-affinity gastrin releasing peptide receptor (GRPR, BBN receptor subtype 2, BB2) has been identified in tissue biopsy samples and immortalized cell lines of many human cancers and is an ideal biomarker for targeting early-stage disease. Early on, the ability of GRPR agonists to be rapidly internalized coupled with a high incidence of GRPR expression on various neoplasias was a driving force for the design and development of new diagnostic and therapeutic agents targeting GRP receptor-positive tumors. Recent reports, however, show compelling evidence that radiopharmaceutical design and development based upon antagonist-type ligand frameworks clearly bears reexamination. Last of all, the ability to target multiple biomarkers simultaneously via a heterodimeric targeting ligand has also provided a new avenue to investigate the dual targeting capacity of bivalent radioligands for improved in vivo molecular imaging and treatment of specific human cancers.

In this report, we describe recent advances in ¹⁷⁷Lu-labeled bombesin peptides for targeted radiotherapy that includes agonist, antagonist, and multivalent cell-targeting agents. In vitro, in vivo translational, and in vivo human clinical investigations are described.

Cite this article as:

Reynolds Stott Tamila, Bandari P. Rajendra, Jiang Zongrun and Smith J. Charles, Lutetium-177 Labeled Bombesin Peptides for Radionuclide Therapy, Current Radiopharmaceuticals 2016; 9 (1) . https://dx.doi.org/10.2174/1874471008666150313112922