title: Synthesis, stabilization and formulation of [177Lu]Lu-AMBA, a systemic radiotherapeutic agent for Gastrin Releasing Peptide receptor positive tumors.
abstract: A robust formulation was developed for [(177)Lu]Lu-AMBA ((177)Lu-DO3A-CH(2)CO-G-[4-aminobenzoyl]-QWAVGHLM-NH(2)), a Bombesin-like agonist with high affinity for Gastrin Releasing Peptide (GRP) receptors. During optimization of labeling, the effect of several radiostabilizers was evaluated; a combination of selenomethionine and ascorbic acid showed superiority over other tested radiostabilizers. The resulting two-vial formulation maintains a radiochemical purity (RCP) of >90% for at least 2 days at room temperature. The method of stabilization should be useful for other methionine-containing peptide radiopharmaceuticals in diagnostic and therapeutic applications.
authors.affiliation: Bracco Research USA Inc., 305 College Road East, Princeton, NJ 08540, USA.
authors.forename: Jianqing
authors.initials: J
authors.lastname: Chen
authors.forename: Karen E
authors.initials: KE
authors.lastname: Linder
authors.forename: Aldo
authors.initials: A
authors.lastname: Cagnolini
authors.forename: Edmund
authors.initials: E
authors.lastname: Metcalfe
authors.forename: Natarajan
authors.initials: N
authors.lastname: Raju
authors.forename: Michael F
authors.initials: MF
authors.lastname: Tweedle
authors.forename: Rolf E
authors.initials: RE
authors.lastname: Swenson
mesh_terms: D004355:Drug Stability; D005615:Freezing; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008024:Ligands; D008187:Lutetium / Q000737:chemistry* / Q000627:therapeutic use; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000627:therapeutic use; D011837:Radiation-Protective Agents / Q000737:chemistry; D011868:Radioisotopes / Q000737:chemistry* / Q000627:therapeutic use; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000627:therapeutic use; D018004:Receptors, Bombesin; D019163:Reducing Agents / Q000737:chemistry; D012645:Selenomethionine / Q000737:chemistry
chemical_list: C512446:DO3A-CH2CO-G-4-aminobenzoyl-Q-W-A-V-G-H-L-M-NH2; D008024:Ligands; D009842:Oligopeptides; D011837:Radiation-Protective Agents; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D018004:Receptors, Bombesin; D019163:Reducing Agents; D008187:Lutetium; D012645:Selenomethionine