Development of a fully automated low-pressure [11 C]CO carbonylation apparatus.

Mélodie Ferrat,Youssef El Khoury,Kenneth Dahl,Christer Halldin,Peter Larsen,Magnus Schou

doi:10.1002/jlcr.3866

Abstract

[11C]carbon monoxide ([11C]CO) is a versatile synthon for radiolabeling of drug‐like molecules for imaging studies with positron emission tomography (PET). We here report the development of a novel, user‐friendly, fully automated, and good manufacturing practice (GMP) compliant low‐pressure synthesis module for 11C‐carbonylation reactions using [11C]CO. In this synthesis module, [11C]CO was reliably prepared from cyclotron‐produced [11C]carbon dioxide ([11C]CO2) by reduction over heated molybdenum and delivered to the reaction vessel within 7 min after end of bombardment, with an overall radiochemical yield (RCY) of 71%. [11C]AZ13198083, a histamine type‐3 receptor ligand, was used as a model compound to assess the functionality of the radiochemistry module. At full batch production conditions (55 μA, 30 min), our newly developed low‐pressure 11C‐carbonylation apparatus enabled us to prepare [11C]AZ13198083 in an isolated radioactivity of 8540 ± 1400 MBq (n = 3). The radiochemical purity of each of the final formulated batches exceeded 99%, and all other quality control tests results conformed with specifications typically set for carbon‐11 labeled radiopharmaceuticals. In conclusion, this novel radiochemistry system offers a convenient GMP compliant production drugs and radioligands for imaging studies in human subjects.

Highlights

The [11C]CO radiochemistry apparatus was designed to handle all parts of a radiopharmaceutical preparation in an integrated, automated, and good manufacturing practice (GMP) compliant fashion
The apparatus is setup for manufacturing according to GMP and comprises all relevant parts of a radiopharmaceutical production, including radiochemistry, purification, formulation, and sterile filtration
The apparatus was successfully applied to the production of the histamine type-3 receptor radioligand [11C]AZ13198083 in high radiochemical yield (RCY) and fulfilling all set quality control (QC) specifications

Summary

Introduction

[11C]carbon monoxide ([11C]CO) has been applied in radiochemistry for several decades, it has not yet gained ground as a mainstream labeling agent in the positron emission tomography (PET) radiochemistry community.[1,2] many important methodological developments have been made that have facilitated its use as a synthon in PET radiochemistry,[3,4,5,6] in particular in transition metal-mediated 11C-carbonylation reactions.[7,8,9,10,11,12] The most explored methodology to date is probably the high-pressure autoclave method,[13] but due to its technically sophisticated setup, the focus has recently been directed to different ways of performing 11C-carbonylation reactions at ambient pressure.[14,15,16]The aim of the current work was to develop a radiochemistry apparatus that would enable application of the recently developed protocol for low-pressure 11C-J Label Compd Radiopharm. 2020;63:517–522.wileyonlinelibrary.com/journal/jlcr FERRAT ET AL.carbonylation reported in our laboratory by Dahl et al.[15]Such an apparatus would be the first commercially available apparatus for this purpose and potentially play an important role in further spreading the use of [11C]CO as a synthon in the PET radiochemistry community. [11C]carbon monoxide ([11C]CO) has been applied in radiochemistry for several decades, it has not yet gained ground as a mainstream labeling agent in the positron emission tomography (PET) radiochemistry community.[1,2] many important methodological developments have been made that have facilitated its use as a synthon in PET radiochemistry,[3,4,5,6] in particular in transition metal-mediated 11C-carbonylation reactions.[7,8,9,10,11,12] The most explored methodology to date is probably the high-pressure autoclave method,[13] but due to its technically sophisticated setup, the focus has recently been directed to different ways of performing 11C-carbonylation reactions at ambient pressure.[14,15,16]. Carbonylation reported in our laboratory by Dahl et al.[15]. Such an apparatus would be the first commercially available apparatus for this purpose and potentially play an important role in further spreading the use of [11C]CO as a synthon in the PET radiochemistry community

Objectives

Results

Conclusion