Automated synthesis of 1-[11C]acetoacetate on a TRASIS AIO module

Abstract

We automated radiochemical synthesis of 1-[¹¹C]acetoacetate in a commercially available radiochemistry module, TRASIS AllInOne by [¹¹C]carboxylation of the corresponding enolate anion generated in situ from isopropenylacetate and MeLi, and purified by ion-exchange column resins.1-[¹¹C]acetoacetate was synthesized with high radiochemical purity (95%) and specific activity (~ 66.6GBq/µmol, n = 30) with 35% radiochemical yield, decay corrected to end of synthesis. The total synthesis required ~ 16min. PET imaging studies were conducted with 1-[¹¹C]acetoacetate in vervet monkeys to validate the radiochemical synthesis. Tissue uptake distribution was similar to that reported in humans.

Keywords: Automation; Formulations; Ion-exchange column; Ketone metabolism; Non-Human primates; PET imaging.

Figure 1

TRASIS AIO reaction program screenshot for [¹¹C]AcAc radiosynthesis. Port#1 [¹¹C]CO₂; Port #2 sterile water setup-hydrolysis; Port #3 reaction vial holder 1; Port# 4 citrate buffer solution (10 mL syringe) 5 mL, pH 4.0; Port#5 sterile water setup-washing AG 1X-8 cartridge; Port#6 reaction mixture syringe (20 mL syringe); Port #7 cartridge holder for Dowex X8-100 (cation exchange resin material); Port#8 cartridge holder for AG 1X-8 (anion exchange resin material); Port#9 reaction vial holder 2 (waste vial); Port#10 product line; Port #11 helium degassing line

Figure 2

TRASIS AIO reaction setup for [¹¹C]AcAc radiosynthesis

Figure 3

a. Whole body PET image b. organ biodistribution through PET- SUV data analysis (n=6) of adult vervet monkey obtained after iv injection of [¹¹C]AcAc (0.3 GBq)

Figure 4

Representative time activity curves (TACs) starting from 0-1800 seconds from a female monkey whole brain injected with [¹¹C]AcAc (0.3 GBq)

Scheme 1

Radiosynthesis of [¹¹C]AcAc