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 (Ebmax = 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.