Automated SPE-based synthesis of 16α-[18F]fluoroestradiol without HPLC purification step

Федорова, О. С.; Nikolaeva, V S; Красикова, Р. Н.

doi:10.1016/j.apradiso.2018.08.007

Cited by 16 publications

(5 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…All of the reagents transfer was achieved through nitrogen flow. The module used is described elsewhere [ 27 ]. In brief, [ 18 F]fluoride was trapped on the QMA cartridge (130 mg) and radioactivity was eluted backwards relative to the loading direction using a solution of TBAOTs in 0.8 mL of MeOH, with the eluate collected directly into the reaction vessel.…”

Section: Resultsmentioning

confidence: 99%

Automated Optimized Synthesis of [18F]FLT Using Non-Basic Phase-Transfer Catalyst with Reduced Precursor Amount

2022

View full text Add to dashboard Cite

3′-deoxy-3′-[18F]fluorothymidine ([18F]FLT) is a positron emission tomography (PET) tracer useful for tumor proliferation assessment for a number of cancers, particularly in the cases of brain, lung, and breast tumors. At present [18F], FLT is commonly prepared by means of the nucleophilic radiofluorination of 3-N-Boc-5′-O-DMT-3′-O-nosyl thymidine precursor in the presence of a phase-transfer catalyst, followed by an acidic hydrolysis. To achieve high radiochemical yield, relatively large amounts of precursor (20–40 mg) are commonly used, leading to difficulties during purification steps, especially if a solid-phase extraction (SPE) approach is attempted. The present study describes an efficient method for [18F]FLT synthesis, employing tetrabutyl ammonium tosylate as a non-basic phase-transfer catalyst, with a greatly reduced amount of precursor employed. With a reduction of the precursor amount contributing to lower amounts of synthesis by-products in the reaction mixture, an SPE purification procedure using only two commercially available cartridges—OASIS HLB 6cc and Sep-Pak Alumina N Plus Light—has been developed for use on the GE TRACERlab FX N Pro synthesis module. [18F]FLT was obtained in radiochemical yield of 16 ± 2% (decay-corrected) and radiochemical purity >99% with synthesis time not exceeding 55 min. The product was formulated in 16 mL of normal saline with 5% ethanol (v/v). The amounts of chemical impurities and residual solvents were within the limits established by European Pharmacopoeia. The procedure described compares favorably with previously reported methods due to simplified automation, cheaper and more accessible consumables, and a significant reduction in the consumption of an expensive precursor.

show abstract

Section: Resultsmentioning

confidence: 99%

Automated Optimized Synthesis of [18F]FLT Using Non-Basic Phase-Transfer Catalyst with Reduced Precursor Amount

2022

View full text Add to dashboard Cite

show abstract

“…Many recent reports describe the SPE purification method for different PET radiotracers. This technique has been successfully applied to prepare a number of clinically relevant radioactive tracers, including [ 18 F]FDG, [ 18 F]FMISO, [ 11 C]PiB, [ 18 F]FMZ, and [ 18 F]FES . An SPE purification method for preparing [ 18 F]AV‐45 ([ 18 F] 5 ) had been previously reported without HPLC purification .…”

Section: Resultsmentioning

confidence: 99%

“…The calibration curves are included in the Supporting information. 24 An SPE purification method for preparing [ 18 F] AV-45 ([ 18 F]5) had been previously reported without HPLC purification. 18 However, the reported SPE purification method did not fully remove the hydroxyl derivative, AV-136, 4, which could potentially interfere with the detection of Aβ plaques in the brain.…”

Section: Chemical Synthesismentioning

confidence: 99%

An improved preparation of [¹⁸F]AV‐45 by simplified solid‐phase extraction purification

Zhang

Yao

et al. 2020

Labelled Comp Radiopharmac

View full text Add to dashboard Cite

Amyvid (florbetapir f18, [18F]AV‐45, [18F]5) was the first FDA‐approved positron emission tomography imaging agent targeting β‐amyloid (Aβ) plaques for assisting the diagnosis of Alzheimer disease. This work aimed to improve the [18F]AV‐45 ([18F]5) preparation by using solid‐phase extraction (SPE) purification. [18F]AV‐45 ([18F]5) was synthesized by direct nucleophilic radiofluorination of O‐tosylated precursor (1 mg) at 120°C in anhydrous dimethyl sulfoxide (DMSO), followed by acid hydrolysis of the N‐Boc protecting group. Purification was accomplished by loading the crude reaction mixture to a cartridge (Oasis HLB 3 cc) and eluting with different combinations of solvents. This method removed the chemical impurity while leaving [18F]AV‐45 ([18F]5) on the cartridge. The final dose was eluted by ethanol. [18F]AV‐45 ([18F]5) was produced within 51 minutes (radiochemical yield 42.7 ± 5.9%, decay corrected, n = 3), and the radiochemical purity was greater than 95%. Total chemical impurity per batch (24.1 ± 2.7 μg per batch) was below the limit described in the package insert of Amyvid, florbetapir f18 (chemical mass: less than 50 μg/dose). In summary, [18F]AV‐45 ([18F]5) was produced efficiently and reproducibly using a cartridge‐based SPE purification. This method brings the process closer for routine preparation, similar to the commercially used [18F]FDG.

show abstract

“…We could routinely obtain FES with molar activities well in excess of 1000 Ci/mmol (37 GBq/μmol) [ 2 ], which were sufficient for in vivo PET imaging [ 40 ]. Following our original publication of the synthesis of FES [ 2 ], alternative routes have been reported, some of which avoid stereochemical issues at C-17 [ 41 , 42 , 43 ] and are more adaptable to automated synthesis systems [ 44 , 45 , 46 ], which were not available when we first developed our synthesis.…”

Section: Fes a Pet Imaging Agent For Estrogen Receptors In Breastmentioning

confidence: 99%

PET Imaging Agents (FES, FFNP, and FDHT) for Estrogen, Androgen, and Progesterone Receptors to Improve Management of Breast and Prostate Cancers by Functional Imaging

Katzenellenbogen

2020

Cancers

View full text Add to dashboard Cite

Many breast and prostate cancers are driven by the action of steroid hormones on their cognate receptors in primary tumors and in metastases, and endocrine therapies that inhibit hormone production or block the action of these receptors provide clinical benefit to many but not all of these cancer patients. Because it is difficult to predict which individuals will be helped by endocrine therapies and which will not, positron emission tomography (PET) imaging of estrogen receptor (ER) and progesterone receptor (PgR) in breast cancer, and androgen receptor (AR) in prostate cancer can provide useful, often functional, information on the likelihood of endocrine therapy response in individual patients. This review covers our development of three PET imaging agents, 16α-[18F]fluoroestradiol (FES) for ER, 21-[18F]fluoro-furanyl-nor-progesterone (FFNP) for PgR, and 16β-[18F]fluoro-5α-dihydrotestosterone (FDHT) for AR, and the evolution of their clinical use. For these agents, the pathway from concept through development tracks with an emerging understanding of critical performance criteria that is needed for successful PET imaging of these low-abundance receptor targets. Progress in the ongoing evaluation of what they can add to the clinical management of breast and prostate cancers reflects our increased understanding of these diseases and of optimal strategies for predicting the success of clinical endocrine therapies.

show abstract

Automated SPE-based synthesis of 16α-[18F]fluoroestradiol without HPLC purification step

Cited by 16 publications

References 18 publications

Automated Optimized Synthesis of [18F]FLT Using Non-Basic Phase-Transfer Catalyst with Reduced Precursor Amount

Automated Optimized Synthesis of [18F]FLT Using Non-Basic Phase-Transfer Catalyst with Reduced Precursor Amount

An improved preparation of [¹⁸F]AV‐45 by simplified solid‐phase extraction purification

PET Imaging Agents (FES, FFNP, and FDHT) for Estrogen, Androgen, and Progesterone Receptors to Improve Management of Breast and Prostate Cancers by Functional Imaging

Contact Info

Product

Resources

About

Automated SPE-based synthesis of 16α-[18F]fluoroestradiol without HPLC purification step

Cited by 16 publications

References 18 publications

Automated Optimized Synthesis of [18F]FLT Using Non-Basic Phase-Transfer Catalyst with Reduced Precursor Amount

Automated Optimized Synthesis of [18F]FLT Using Non-Basic Phase-Transfer Catalyst with Reduced Precursor Amount

An improved preparation of [18F]AV‐45 by simplified solid‐phase extraction purification

PET Imaging Agents (FES, FFNP, and FDHT) for Estrogen, Androgen, and Progesterone Receptors to Improve Management of Breast and Prostate Cancers by Functional Imaging

Contact Info

Product

Resources

About

An improved preparation of [¹⁸F]AV‐45 by simplified solid‐phase extraction purification