Automated synthesis, characterization and biological evaluation of [68Ga]Ga-AMBA, and the synthesis and characterization of natGa-AMBA and [67Ga]Ga-AMBA

Ga-AMBA (Ga-DO3A-CH2CO-G-[4-aminobenzoyl]-QWAVGHLM-NH2) is a bombesin-like agonist with high affinity for gastrin releasing peptide receptors (GRP-R) Syntheses for Ga-nat-AMBA, [Ga-67]Ga-AMBA and [Ga-68]Ga-AMBA were developed. The preparation of HPLC-purified and Sep-Pak purified [Ga-68]Ga-AMBA were fully automated, using the built-in radiodetector of the Tracerlab FX F-N synthesizer to monitor fractionated Ge-68/Ga-68 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 [Ga-68]Ga-AMBA. Both [Ga-67]Ga-AMBA and [Lu-177]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. 044 +/- 0.08 nM), high internalization (78, 77%) and low efflux from cells at 2 h (2.4 +/- 07: 2.9 +/- 1.8%) Biodistribution results in PC-3 tumor-bearing male nude mice showed comparable uptake for [Lu-177]Lu-. [In-111]In-. [Ga-67]Ga- and [Ga-68]Ga-AMBA. (c) 2010 Elsevier Ltd. All rights reserved.