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

Joshi, Raman Kumar; Goud, Nerella Sridhar; Nagaraj, Chandana; Kumar, Dilip; Gopinath, R.; Rao, Naren P.; Dhawan, Anju; Bhattacharya, Alok; Mangalore, Sandhya; Bharath, Rose Dawn; Kumar, Pardeep

doi:10.1016/j.apradiso.2020.109486

Cited by 14 publications

(33 citation statements)

References 10 publications

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“…The radionuclide purity was more than 95%, and a half-life of 111 ± 4 min proved the radionuclide identity as 18 F with 511 keV peak as a significant peak. As evaluated by previously described methods, the kryptofix levels were below 50 µg/mL 17 . The concentration of residual solvent DMF was 80 ± 8 ppm (reference value-810 ppm).…”

Section: Resultsmentioning

confidence: 99%

“…The retention time of the cold AVT-011 standard was measured at λ max 254 nm using a UV-Vis detector, whereas the [ 18 F]AVT-011 (07) was detected using the radioactive detector. The quality control parameters like physical appearance, pH, radiochemical purity, radionuclide purity, chemical purities, residual solvents, sterility, endotoxin test, and stability (in-vitro) were done as per the standard protocol described elsewhere 17 .…”

Section: Quality Controlmentioning

confidence: 99%

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

Kumar

Thakur

Acharya

et al. 2022

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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.

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Section: Resultsmentioning

confidence: 99%

Section: Quality Controlmentioning

confidence: 99%

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

Kumar

Thakur

Acharya

et al. 2022

Sci Rep

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“…The clinically used PET radiotracers like [ 18 F]FDG, 18 F-FLT, 18 F-FES, and 18 F-choline were synthesized using nucleophilic radiofluorination reactions with 18 F-fluoride, from which the synthesis of [ 18 F]FDG was shown in Figure 7B (59). Many automated synthesis modules and methodologies are developed based on nucleophilic radiofluorination (60,61). Recently one study reported first transition metal assisted 18 F-labeling of heteroaromatic phenols through deoxyfluorination process via Ruthenium π-complexes.…”

Section: The Chemistry Of Radiolabeling With Fluorine-18 and Carbon-1...mentioning

confidence: 99%

PET Molecular Imaging in Drug Development: The Imaging and Chemistry Perspective

et al. 2022

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Positron emission tomography with selective radioligands advances the drug discovery and development process by revealing information about target engagement, proof of mechanism, pharmacokinetic and pharmacodynamic profiles. Positron emission tomography (PET) is an essential and highly significant tool to study therapeutic drug development, dose regimen, and the drug plasma concentrations of new drug candidates. Selective radioligands bring up target-specific information in several disease states including cancer, cardiovascular, and neurological conditions by quantifying various rates of biological processes with PET, which are associated with its physiological changes in living subjects, thus it reveals disease progression and also advances the clinical investigation. This study explores the major roles, applications, and advances of PET molecular imaging in drug discovery and development process with a wide range of radiochemistry as well as clinical outcomes of positron-emitting carbon-11 and fluorine-18 radiotracers.

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“…[ 11 C]Acyl chloride or aryl acid chloride can be synthesized from [ 11 C]carbon dioxide using an appropriate Grignard reagent followed by subsequent chlorination using either thionyl chloride or phthaloyl dichloride. , [ 11 C]Methyl iodide is another commonly used secondary agent. A common method of generating [ 11 C]methyl iodide is the reduction of [ 11 C]carbon dioxide with lithium aluminum hydride (LAH) followed by subsequent iodination by hydroiodic acid treatment; another method has been reported through gas-phase iodination of [ 11 C]methane for [ 11 C]methyl iodide synthesis. , [ 11 C]Nitromethane is synthesized from [ 11 C]methyl iodide by passing over heated silver nitrite at 80 °C, and [ 11 C]methyl isocyanate is generated from [ 11 C]methyl iodide by passing over heated silver cyanate at 180 °C . The [ 11 C]methyl triflate is also generated from [ 11 C]methyl iodide by passing over heated silver triflate at 200 °C, and [ 11 C]methyl iodide can be converted into [ 11 C]carbon disulfide by passing over sulfur through a column and sand at 500 °C …”

Section: Introductionmentioning

confidence: 99%

“…40,41 [ 11 C]-Nitromethane is synthesized from [ 11 C]methyl iodide by passing over heated silver nitrite at 80 °C, 42 and [ 11 C]methyl isocyanate is generated from [ 11 C]methyl iodide by passing over heated silver cyanate at 180 °C. 43 The [ 11 C]methyl triflate is also generated from [ 11 C]methyl iodide by passing over heated silver triflate at 200 °C, 44 and [ 11 C]methyl iodide can be converted into [ 11 C]carbon disulfide by passing over sulfur through a column and sand at 500 °C.…”

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confidence: 99%

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

et al. 2021

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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 (t 1/2 = 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.

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

Cited by 14 publications

References 10 publications

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

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

PET Molecular Imaging in Drug Development: The Imaging and Chemistry Perspective

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

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