title: Automated synthesis, characterization and biological evaluation of [(68)Ga]Ga-AMBA, and the synthesis and characterization of (nat)Ga-AMBA and [(67)Ga]Ga-AMBA.
abstract: Ga-AMBA (Ga-DO3A-CH(2)CO-G-[4-aminobenzoyl]-QWAVGHLM-NH(2)) is a bombesin-like agonist with high affinity for gastrin releasing peptide receptors (GRP-R). Syntheses for (nat)Ga-AMBA, [(67)Ga]Ga-AMBA and [(68)Ga]Ga-AMBA were developed. The preparation of HPLC-purified and Sep-Pak purified [(68)Ga]Ga-AMBA were fully automated, using the built-in radiodetector of the Tracerlab FX F-N synthesizer to monitor fractionated (68)Ge/(68)Ga generator elution and purification. The total synthesis time, including the fractional elution of the generator, was 20 min for Sep-Pak purified material and 40 min for HPLC-purified [(68)Ga]Ga-AMBA. Both [(67)Ga]Ga-AMBA and [(177)Lu]Lu-AMBA showed comparable high affinity for GRP-R in the human prostate cancer cell line PC-3 in vitro (k(D)=0.46+/-0.07; 0.44+/-0.08 nM), high internalization (78; 77%) and low efflux from cells at 2 h (2.4+/-0.7; 2.9+/-1.8%). Biodistribution results in PC-3 tumor-bearing male nude mice showed comparable uptake for [(177)Lu]Lu-, [(111)In]In-, [(67)Ga]Ga- and [(68)Ga]Ga-AMBA.
authors.affiliation: Ernst Felder Laboratories, Bracco Research USA Inc., 305 College Road East, Princeton, NJ 08540, USA.
authors.forename: Aldo
authors.initials: A
authors.lastname: Cagnolini
authors.forename: Jianqing
authors.initials: J
authors.lastname: Chen
authors.forename: Kimberly
authors.initials: K
authors.lastname: Ramos
authors.forename: Tina Marie
authors.initials: TM
authors.lastname: Skedzielewski
authors.forename: Laura E
authors.initials: LE
authors.lastname: Lantry
authors.forename: Adrian D
authors.initials: AD
authors.lastname: Nunn
authors.forename: Rolf E
authors.initials: RE
authors.lastname: Swenson
authors.forename: Karen E
authors.initials: KE
authors.lastname: Linder
mesh_terms: D000818:Animals; D001331:Automation; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D005710:Gallium Radioisotopes / Q000737:chemistry*; D006801:Humans; D008297:Male; D051379:Mice; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism
chemical_list: C512446:DO3A-CH2CO-G-4-aminobenzoyl-Q-W-A-V-G-H-L-M-NH2; D005710:Gallium Radioisotopes; D009842:Oligopeptides