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

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.

Development of an economical method to synthesize O-(2-[18 F]fluoroethyl)-L-tyrosine (18 FFET).

Positron emission tomography (PET) using O-(2-[18 F]fluoroethyl)-L-tyrosine ([18 F]FET) has shown great success in differentiating tumor recurrence from necrosis. In this study, we are reporting the experience of synthesis [18 F]FET by varying the concentration of TET precursor in different chemistry modules. TET precursor (2-10 mg) was used for the synthesis of [18 F]FET in an automated (MX Tracerlab) module (n = 6) and semiautomated (FX2N Tracerlab) module (n = 19). The quality control was performed for all the preparations. For human imaging, 220 ± 50 MBq of [18 F]FET was briefly injected into the patient to acquire PET-MR images. The radiochemical purity was greater than 95% for the final product in both modules. The decay corrected average yield was 10.7 ± 4.7% (10 mg, n = 3) and 8.2 ± 2.6% (2 mg, n = 3) with automated chemistry module and 36.7 ± 7.3% (8-10 mg, n = 12), 26.4 ± 3.1% (5-7 mg, n = 4), and 35.1 ± 3.8% (2-4 mg, n = 3) with semiautomated chemistry modules. The PET imaging showed uptake at the lesion site (SUVmax = 7.5 ± 2.6) and concordance with the MR image. The [18 F]FET was produced with a higher radiochemical yield with 2.0 mg of the precursor with substantial yield and is suitable for brain tumor imaging.

Synthesis, characterization, and radiosynthesis of fluorine-18-AVT-011 as a Pgp chemoresistance imaging marker.

P-glycoprotein (Pgp) is the most studied ATP-binding cassette (ABC) efflux transporter and contributes to chemoresistance. A few tracers have been developed to detect the in-vivo status of chemoresistance using positron emission tomography (PET) imaging. In our study, we have synthesized labeled AVT-011 with fluorine-18 (18F) followed by in-vitro and in-vivo analysis. Tosylate AVT-011 precursor was synthesized and characterized by 1H-NMR and 13C-NMR. AVT-011 was labeled with 18F using the nucleophilic substitution method, and a standard set of quality control was performed. The specificity for Pgp was tested in U87MG cells with and without an inhibitor (tariquidar). The biodistribution and in-vivo stability were tested in the small animals (mice). The biodistribution data of [18F]-AVT-011 was extracted from the PET-CT imaging of breast cancer patients (n = 6). The precursor was synthesized with 36 ± 4% yield and 97 ± 2% purity. The labeling was more than 95% with a 42 ± 2% yield, as evaluated by Radio-HPLC. The cell-binding assay showed a specificity of the tracer for Pgp as the uptake increased by twice after blocking the Pgp receptors. The radiotracer showed a hepatorenal excretion pathway for clearance in an animal study. The uptake was higher in the liver, lungs, spleen, and heart at 15 min and decreased at 60 min. The patients' distribution showed similar uptake patterns as observed in the small animals. [18F]AVT-011 was characterized successfully with high radiochemical purity and yield. The in-vitro and in-vivo studies proved its specificity for Pgp and safe for patient use.