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.

Carbon-11: Radiochemistry and Target-Based PET Molecular Imaging Applications in Oncology, Cardiology, and Neurology.

The positron emission tomography (PET) molecular imaging technique has gained its universal value as a remarkable tool for medical diagnosis and biomedical research. Carbon-11 is one of the promising radiotracers that can report target-specific information related to its pharmacology and physiology to understand the disease status. Currently, many of the available carbon-11 (t1/2 = 20.4 min) PET radiotracers are heterocyclic derivatives that have been synthesized using carbon-11 inserted different functional groups obtained from primary and secondary carbon-11 precursors. A spectrum of carbon-11 PET radiotracers has been developed against many of the upregulated and emerging targets for the diagnosis, prognosis, prediction, and therapy in the fields of oncology, cardiology, and neurology. This review focuses on the carbon-11 radiochemistry and various target-specific PET molecular imaging agents used in tumor, heart, brain, and neuroinflammatory disease imaging along with its associated pathology.

Radiosynthesis challenges of 11C and 18F-labeled radiotracers in the FX2C/N tracerlab and their validation through PET-MR imaging.

Glucose is the renowned source of the energy for the cancer growth, that's the reason for [18F]FDG success and make it widely used radiotracer. Though [18F]FDG has its own inherent limitations therefore many tracers have been developed to target specific receptors, and other metabolic routes. We have used FX2C and FX2N Tracerlab modules for the synthesis of the [11C]methionine, [18F]choline and [18F]fluorodopa via nucleophilic pathway in FX2C/N module. [11C]methionine was standardized in FX2C module using two different precursors, and purified using C18 cartridge based technique. [18F]methylcholine was synthesized using dimethylaminoethanol precursor and purified using cartridge-based method. [18F]fluorodopa was synthesized using nucleophilic precursor and purified using in-built preparative HPLC on FX2N module. All radioactive intermediates and chemical impurities were evaluated by analytical HPLC. The radiochemical purity of D and L-[11C]methionine were 4.6 ± 3.2% and 95.4 ± 3.6% while other chemical impurities were less than prescribed limits with yield of 20 ± 5%. [18F]fluoromethylcholine was prepared with high radiochemical purity of 97.3 ± 2.6% with yield of 8 ± 3%. [18F]fluorodopa was synthesized with high radiochemical purity of 95.8 ± 1.4% with 15 ± 3% yield. The adaptation of [18F]fluorodopa synthesis to FX2N module via designing synthesis sequence and purified through on-line HPLC has provided high radiochemical purity. PET-MR imaging was done using these tracers which have validated the synthesis and their availability for future clinical applications.

Fluorine-18: A radionuclide with diverse range of radiochemistry and synthesis strategies for target based PET diagnosis.

Fluorine-18 is one of the most widely used radionuclides for the production of radiopharmaceuticals for positron emission tomography (PET). The radiolabeling methods like nucleophilic, electrophilic, Cu mediated mechanisms or prosthetic groups are widely using to achieve high regioselective radiochemical yields. It acts as a powerful tool to identify new drug targets through cellular uptake, pharmacokinetic (ADME) and pharmacodynamic parameters of the 18F labeled tracer or drug. These PET tracers have been developed based on the receptors expressed in a disease condition. A number of 18F radiotracers have been developed against the Tropomyosin Receptor Kinases (Trks), Carbonic anhydrases (CAs), Epidermal Growth Factor Receptors (EGFR), Poly ADP ribose polymerase (PARP) etc. for the diagnosis in cancer therapy. The current research also focused on the development of novel 18F radiotracers for neurological conditions for deciphering underlying physiology in diseases like Alzheimer, and Parkinson. Therefore, in this review we have focused on 18F labeling methods, and radiotracers developed against common cancers and neurological conditions.

Troubleshooting for F-18 Fluorocholine Synthesis: An Institutional Experience.

Choline is a natural substrate for phospholipid synthesis. F-18 labeled fluorocholine nowadays is routinely used for imaging brain tumors, parathyroid adenoma, and prostate cancer. It is synthesized through nucleophilic substitution reaction using dibromomethane and N, N-dimethylaminoethanol as primary and secondary precursors, respectively. However, sometimes, failures are encountered in F-18 fluorocholine production. Few problems and troubleshooting during synthesis are discussed here.

In-house Preparation and Quality Control of Tc99m TRODAT 1 for Diagnostic Single-photon Emission Computed Tomography/Computed Tomography Imaging in Parkinson's Disease.

PURPOSE OF STUDY: Loss of dopamine neurons in the brain is a characteristic feature of Parkinson's disease (PD). TRODAT-1 is a tropane derivative that binds to dopamine transporter (DAT) receptors. It can be used for noninvasive in vivo imaging of DAT receptors leading to the early detection of PD. The present study aims to optimize the in-house radiolabeling of TRODAT-1 with Tc-99 m in hospital radiopharmacy set up along with performing single-photon emission computed tomography/computed tomography imaging in patients with PD. MATERIALS AND METHODS: Radiolabeling was performed through transchelation method. For optimization studies, varied amount of glucoheptonate (GHA) and stannous chloride was incubated with Tc-99 m for 10 min at room temperature. TRODAT-1 was added to the reaction mixture followed by incubation at 95°C for various time intervals. Phosphate buffer saline was added to maintain the pH of the final product. After performing the quality checks, whole-body imaging was performed to check the biodistribution in 4 patients at 1 h postinjection of 20-25 mCi (740-925 MBq) of Tc-99 m-TRODAT-1. Regional brain imaging was performed at 3-4 h. Clinical evaluation was done in control (n = 5) and in patients with PD (n = 5). RESULTS: Radiolabeling yield of 100% was achieved by incubating TRODAT-1 with Tc-99 m GHA. All the quality control indicated the suitability of radiopharmaceutical for the intravenous administration. Good uptake of Tc-99 m TRODAT-1 was observed in the striatum of normal patients. However, decreased uptake was seen in patients with PD. CONCLUSION: Tc-99 m TRODAT-1 is a potential radiopharmaceutical for the diagnosis and staging PD which can be radiolabeled in-house with good yield leading to its easy availability.