Standardization and Clinical Use of a Single-vial Formulation of Technetium-99m-Trodat Using Autoclave Method

Abstract

Background: Parkinson's disease (PD) is characterized by the degeneration of dopaminergic neurons in the substantia nigra. SPECT imaging using technetium-99m [^99mTc] labeled trodat is the choice of imaging to differentiate PD from its other forms like drug-induced PD.

Aims and objectives: The main objective of our study was to prepare in-house sterile formulation of [^99mTc]Tc-trodat and use in clinics.

Materials and methods: The labeling of trodat was standardized using glucoheptonate sodium salt (GHA), stannous chloride dihydrate (in 0.05 N HCl), and ethylenediaminetetraacetic acid (Na-EDTA). The preparation was mixed and autoclaved at 15 psi for 15 min. The standardised formulation was stored at 4°C, -20°C and -80°C and labeling with ^99mTc was tested for up to 6 days. The radiochemical purity, chemical impurities, and endotoxin levels were tested. The frozen formulation was tested in swiss mice (n = 3) for biodistribution studies at 4 h. Around 18 ± 2 mCi was injected intravenously in each patient (n = 5) and the image was acquired at 4 h post-injection.

Results: The radiochemical purity of the preparation was 98.3 ± 1.4% with a retention time of 16.8 ± 1.5 min as compared to 4.0 ± 0.5 min for free ^99mTc. Animal distribution showed highest uptake in liver and dual excretion via hepatobiliary and renal system. [^99mTc]Tc-trodat imaging was able to differentiate both caudate and putamen.

Conclusions: In-house frozen preparation was advantageous, as it has decreased the chance of manual error as compared to daily make up formulations and economical as compared to commercially available kits.

Keywords: Parkinson’s disease; single-photon emission computed photography; technetium-99m; trodat.

Figure 1

Effect of concentration of the glucoheptonate on the labeling of the TRODAT with (Technetium-99m). GHA: Glucoheptonate

Figure 2

Radio-high-performance liquid chromatography peak for (Technetium-99m [^99mTc])-Trodat at 16.6 min and free (^99mTc) at 4.3 min

Figure 3

Correlation between high-performance liquid chromatography (HPLC) and thin-layer chromatography technique for measuring labeling efficiency (a) when HPLC showed labeling >95% (b) when HPLC showed labeling efficiency <90%

Figure 4

Biodistribution of (Technetium-99m)-TRODAT in mice at 240 min postinjection

Figure 5

(Technetium-99m)-TRODAT biodistribution in humans

Figure 6

(a) Uptake in brain, uptake can be seen in caudate and putamen regions. (b) Radio-high-performance liquid chromatography peak for (Technetium-99m)-TRODAT proving in vivo stability at 4 h