Determination of radionuclides and radiochemical impurities produced by in-house cyclotron irradiation and subsequent radiosynthesis of PET tracers

Kiichi Ishiwata,Masanari Sakai,Hideaki Hasegawa,Kunpei Hayashi,Jun Toyohara,Sugio Kawauchi

doi:10.1007/s12149-016-1134-3

Abstract

ObjectiveTo elucidate the radionuclides and radiochemical impurities included in radiosynthesis processes of positron emission tomography (PET) tracers.MethodsTarget materials and PET tracers were produced using a cyclotron/synthesis system from Sumitomo Heavy Industry. Positron and γ-ray emitting radionuclides were quantified by measuring radioactivity decay and using the high-purity Ge detector, respectively. Radiochemical species in gaseous and aqueous target materials were analyzed by gas and ion chromatography, respectively.ResultsTarget materials had considerable levels of several positron emitters in addition to the positron of interest, and in the case of aqueous target materials extremely low levels of many γ-emitters. Five 11C-, 15O-, or 18F-labeled tracers produced from gaseous materials via chemical reactions had no radionuclidic impurities, whereas 18F-FDG, 18F-NaF, and 13N-NH3 produced from aqueous materials had several γ-emitters as well as impure positron emitters. 15O-Labeled CO2, O2, and CO had a radionuclidic impurity 13N-N2 (0.5–0.7 %).ConclusionsTarget materials had several positron emitters other than the positron of interest, and extremely low level γ-emitters in the case of aqueous materials. PET tracers produced from gaseous materials except for 15O-labeled gases had no impure radionuclides, whereas those derived from aqueous materials contained acceptable levels of impure positron emitters and extremely low levels of several γ-emitters.

Highlights

The quality assurance of positron-emitting tracers used in positron emission tomography (PET) is performed in accordance with guidance documents such as United States Pharmacopeia/National Formulary (USP/NF) and European Pharmacopeia (EP)
Five 11C, 15O, or 18F-labeled tracers produced from gaseous materials via chemical reactions had no radionuclidic impurities, whereas 18F-FDG, 18F-NaF, and 13N-NH3 produced from aqueous materials had several c-emitters as well as impure positron emitters
PET tracers produced from gaseous materials except for 15O-labeled gases had no impure radionuclides, whereas those derived from aqueous materials contained acceptable levels of impure positron emitters and extremely low levels of several c-emitters

Summary

Introduction

The quality assurance of positron-emitting tracers used in positron emission tomography (PET) is performed in accordance with guidance documents such as United States Pharmacopeia/National Formulary (USP/NF) and European Pharmacopeia (EP). Ann Nucl Med (2017) 31:84–92 and 13N are usually produced by proton irradiation of 18OH2O and 16O-H2O, respectively, and it is well known that these aqueous target solutions contain very small amounts of c-emitters with a longer half-life than 18F (109.8 min) [2 and references therein] Most of these impurities are excluded from the final injections, but some impurities potentially remained in the preparation processes without purification using distillation or high-performance liquid chromatography (HPLC). Their levels may be much lower than that of 18F or 13N of interest, and the criteria for radionuclidic purity of PET tracers such as 18F-FDG and 18F-NaF required by the USP/NF (no less than 99.5 %)

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