Short communicationElectrochemistry of pertechnetate on ultramicroelectrode: A new quality control for radiopharmaceuticals manufactured at hospital in nuclear medicine
Introduction
Radiotracers in nuclear medicine are widely used in scintigraphy, single-photon emission computed tomography (SPECT) and positron emission tomography (PET) imaging, for diagnostic investigations [1]. Among them, metastable technetium (99mTc) is one of the most attractive radionuclides to nuclear physicians because of its gamma radioactivity, short half-life (about 6 h), and is rapidly eliminated from the body [2]. Another advantage is its easy in-house production and use via a 99Mo/99mTc generator to produce on demand sodium pertechnetate Na99mTcO4 (noted NaTcO4 thereafter) dissolved in physiological serum [3].
Every day, tens of thousands of radiopharmaceutical injections labeled with NaTcO4 are performed worldwide where NaTcO4 is used in more than 80% cases. Pharmaceuticals are sold lyophilized in sterile kit preparations. Their labeling with NaTcO4 freshly synthesized is made easy and fast via the use of a cold kit containing the pharmaceutical (sealed under nitrogen atmosphere) by adding it with a syringe.
During the labeling, colloidal formation of 99mTcO2⋅xH2O (noted TcO2 thereafter) can occur due to oxygen trace, limiting the labeling yield. TcO2 is considered as an impurity in solution because it is not involved in the radiopharmaceutical labeling. Moreover, it is an excess of radioactivity injected to patient which is useless to imaging diagnostic. Only solutions not less than 95% of radiochemical purity (%RCP) are injected according to the European Pharmacopeia. The %RCP is the percent of NaTcO4 bound to a ligand without any impurity.
Consequently, many quality controls estimating the radiochemical purity defined as the ratio between the activity of the labeled radiopharmaceutical and the total recovered activity are needed every day in nuclear medicine departments. Recommended control quality use chromatography technique such as thin-layer (TLC) and paper chromatographies (PC), but are time consuming and operator dependent (almost 2 h per radiopharmaceutical). No faster analytical technique is used nowadays at hospital. The main reason is the very low concentration of NaTcO4 in samples which is a challenge for titration. The second drawback is the complicated speciation of technetium in solution [4], [5]. The labeling step requires reducing Tc(VII) to a lower state Tc(IV). This is reached with SnCl2•2H2O present in cold kits [6]. In addition to impurities such as free ligands and TcO2, SnO2 can be present too.
Electrochemical techniques could be useful for quality controls in nuclear medicine as an alternative to time-consuming PC tests for quality control of NaTcO4-based injections. Herein, we demonstrate the relevance of using platinum ultramicroelectrodes (UMEs) coupled to stripping technique for titration of pertechnetate trace in saline isotonic solution.
Section snippets
Experimental
Sterile saline infusions were from B. Braun Medical SAS, France, and glass homemade UMEs were rinsed using ultrapure water (Milli-Q, Millipore). 3,3-Diphosphono-1,2-propanedicarbonic acid (DPD, also known as Teceos) and Stamicis ligands used as radiopharmaceutical labeled with NaTcO4 are included in the cold kit from BioCis, France. Myoview is from GE Healthcare, France. Methylethylketon (MEK) and acetonitrile are from VWR (France).
The UMEs consist in Pt wires of 5 and 76 μm diameter
Results and discussion
The electrochemistry of the pertechnetate-based aqueous electrolytes is rich. First studies date back to the seventies from the previous century (if we except Pourbaix diagram works) [7], and many have been performed extensively by polarography in alkaline or acidic medium [8], [9]. On millimeter size glassy carbon electrode, the two oxidation states Tc(IV) and Tc(VII) are observed [10]. Due to the millimeter size of the electrode, detection of species with concentration lower than 10− 7 M is
Conclusion
Several radiopharmaceuticals such as Teceos, Stamicis, and Myoview labeled with NaTcO4 were successfully titrated in physiological serum by electrochemistry on Pt UME. The size of the electrode allows titrations of the radiopharmaceuticals with reproducibility and good sensitivity. In the light of results obtained and compared by DPSV and PC techniques on the same solutions, the Pt UME can be used to redefine a new protocol for quality control of pertechnetate-based solutions injected to
Conflict of interest
There is no conflict of interest.
Acknowledgements
This present work was financially supported by FEDER (grant no 2011-453) and the PRES between the Universities of Burgundy and Franche-Comté, France. We gratefully acknowledge support by the Imagery department in Nuclear Medicine of the University Hospital Center CHU Jean Minjoz.
References (14)
- et al.
History of nuclear medicine and molecular imaging
- et al.
Determination of Sn(II) in technetium cold kits by voltammetry at the hanging mercury drop electrode (HMDE) and relevant radiopharmaceutical applications
Nucl. Med. Biol.
(1998) - et al.
Electrochemical studies of technetium at a mercury electrode
Anal. Chim. Acta.
(1979) Electrochemical behaviour of technetium(VII) in acidic medium
J. Electroanal. Chem. Interfacial Electrochem.
(1979)- et al.
Mechanism and kinetics of the stepwise voltammetric reduction of pertechnetate in alkaline solution to Tc(VI, Tc(V) and Tc(IV)
J. Electroanal. Chem. Interfacial Electrochem.
(1987) Quantitative analytical assay of small amounts of technetium by stripping chronopotentiometry at a glassy carbon electrode
J. Electroanal. Chem. Interfacial Electrochem.
(1988)Electrochemistry of technetium
Int. J. Appl. Radiat. Isot.
(1982)
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