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. 2024 Dec 28;18(1):26.
doi: 10.3390/ph18010026.

Comparison of ZnS(Ag) Scintillator and Proportional Counter Tube for Alpha Detection in Thin-Layer Chromatography

Marc Pretze  1 , Jan Wendrich  2 , Holger Hartmann  1 , Robert Freudenberg  1 , Ralph A Bundschuh  1 , Jörg Kotzerke  1 , Enrico Michler  1
Affiliations

Comparison of ZnS(Ag) Scintillator and Proportional Counter Tube for Alpha Detection in Thin-Layer Chromatography

Marc Pretze et al. Pharmaceuticals (Basel). .

Abstract

(1) Background: Targeted alpha therapy is an emerging field in nuclear medicine driven by two advantages: overcoming resistance in cancer-suffering patients to beta therapies and the practical application of lower activities of 212Pb- and 225Ac-labelled peptides to achieve the same doses compared to beta therapy due to the highly cytotoxic nature of alpha particles. However, quality control of the 212Pb/225Ac-radiopharmaceuticals remains a challenge due to the low activity levels used for therapy (100 kBq/kg) and the formation of several free daughter nuclides immediately after the formulation of patient doses; (2) Methods: The routine alpha detection on thin-layer chromatograms (TLC) of 212Pb- and 225Ac-labelled peptides using a MiniScanPRO+ scanner combined with an alpha detector head was compared with detection using an AR-2000 scanner equipped with an open proportional counter tube. Measurement time, resolution and validity were compared for both scanners; (3) Results: For 225Ac, the quality control values of the radiochemical purity (RCP) were within the acceptance criteria 2 h after TLC development, regardless of when the TLC probe was taken. That is, if the TLC probe was taken 24 h after radiosynthesis, the true value of the RCP was not measured until 5 h after TLC development. For 212Pb-labelled peptides, the probe sampling did not have a high impact on the value of the RCP for the MiniScanPRO+ and AR-2000. A difference was observed when measuring TLC with the AR-2000 in different modes; (4) Conclusions: The MiniScanPRO+ is fast, does not require additional equipment and can also measure the gamma spectrum, which may be important for some radiopharmaceutical production sites and regulatory authorities. The AR-2000 has a better signal-to-noise ratio, and this eliminates the need for additional waiting time after TLC development.

Keywords: 212Pb; 225Ac; PSMA; TATE; TOC; quality control; thin-layer chromatography (TLC).

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Conflict of interest statement

The MiniScanPRO+ and AR-2000 were provided by Eckert & Ziegler, especially for the evaluation of α-particles on TLC. J.W. is employed by Eckert & Ziegler, which has a financial interest in the distribution of TLC scanners. The authors declare no further conflicts of interest.

Figures

Figure 1
Figure 1
Decay diagram for the mother nuclides 225Ac and 224Ra (red square). Shown are their daughter nuclides with half-life (tn = trillion) and stable nuclides (black square), type of decay and the corresponding decay energy and important γ energies for imaging and identification in γ spectrum analyses. The arrows indicate the main decay of the nuclide. 212Bi has two major decays, the probability of which is given in percent (red) by the arrows.
Figure 2
Figure 2
Representative radio-TLCs measured with the MiniScanPro+ at different time points: (A) citrate, (E) NH4Ac—TLC probe taken within 5 min after synthesis—measurement immediately after development; (B) citrate, (F) NH4Ac—TLC probe taken 24 h later—measurement immediately after development; (C) citrate, (G) NH4Ac—TLC probe taken 24 h later—measurement 2 h after development; (D) citrate, (H) NH4Ac—TLC probe taken 24 h later—measurement 24 h after development.
Figure 3
Figure 3
Representative radio-TLCs measured with the AR-2000 at different time points and measurement modes—probe taken immediately after synthesis: (A) alpha detection, 5 min after development; (B) alpha detection, 4 h after development (213Bi is decayed) (C) beta detection, 5 min after development—free 213Bi and 213Bi-PSMA have higher signals in beta mode (440 keV); (D) beta detection, 4 h after development.
Figure 4
Figure 4
Representative radio-TLCs measured 5 min after development in citrate buffer—probe taken immediately after synthesis; (A) measured with the MiniScanPRO+, (B) measured with the AR-2000 in alpha mode, 212Pb-signal was lower at the front compared to measurement (A).
Figure 5
Figure 5
Representative radio-TLCs measured 5 min after development with AR-2000—probe taken immediately after synthesis; (A) TLC in citrate buffer with alpha detection—measuring 8% free 212Bi; (B) TLC in citrate buffer with beta detection—measuring 7% free 212Pb (238 keV) and free 212Bi (2.2 MeV); (C) TLC in NH4Ac with alpha detection—measuring 24% colloidal 212Bi; (D) TLC in NH4Ac with beta detection—measuring 8% colloidal 212Pb and 212Bi.
Figure 6
Figure 6
Respective gamma spectra measured with the MCA of the MiniScanPro+ for verification of the radio nuclidic purity. Gamma energy found given in keV (percentage of probability): (A) 225Ac: 78 keV (3%), 221Fr: 218 keV (12%), 213Bi: 440 keV (26%); (B) 212Pb: 75, 238 keV; 208Tl: 510 (22.6%), 583 (85.0%), 860 (12.5%) keV; 212Bi: 727 (6.7%) keV.
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