Elsevier

Electrochemistry Communications

Volume 51, February 2015, Pages 76-80
Electrochemistry Communications

Short communication
Electrochemistry of pertechnetate on ultramicroelectrode: A new quality control for radiopharmaceuticals manufactured at hospital in nuclear medicine

https://doi.org/10.1016/j.elecom.2014.12.011Get rights and content

Highlights

  • Platinum ultramicroelectrodes coupled to differential pulse stripping voltammetry as an alternative to conventional quality control for radiopharmaceuticals in nuclear medicine.

  • Detection limits of 5 nM with fast experiments can be achieved in less than 2 min.

  • Pt ultramicroelectrode has an excellent signal-to-background characteristic to study the electrochemical behavior of analytes in physiological serum such as NaTcO4 and radiopharmaceuticals.

  • Setup can be used as generic to other radiopharmaceuticals having an electrochemical activity at a potential different from each others. Pt electrodes can be embedded in microsystems for fast and safe control quality monitoring.

Abstract

Every day, thousands of diagnostic tests in nuclear medicine are performed on patients around the world wherein pertechnetate-based solutions are taken internally, requiring time-consuming quality controls. In this paper, we demonstrate the use of platinum ultramicroelectrodes coupled to differential pulse stripping voltammetry as an advantageous alternative to conventional quality control for radiopharmaceuticals using paper or thin-layer chromatography and gamma camera. Detection limits lower than 5 nM have been achieved during fast experiments in few minutes with ready-to-use pertechnetate-based physiological solutions. This method can be generic and transposed to other radiopharmaceuticals having an electrochemical activity at a potential different from each others.

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)

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    Other authors, who studied determination of Tc species by means of electrochemical methods, reported TcO4- detection limits in the range of 10−8 ÷ 10−7 M TcO4− for various types of electrodes: wax-impregnated graphite [12], static mercury drop [13], TOPO/glassy carbon [14]; glassy carbon [15] and hanging mercury drop [16] electrodes. The TcO4− detection limit at the level of 10−9 M was reported in a recently published paper which deals with application of platinum ultramicroelectrodes and differential pulse stripping voltammetry in deterimation of pertechnetates in serum [17]. There are no reported studies on pertechnetates quantification using other types of solid electrodes often used in electrochemistry, such as Au.

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