Radiolysis of 2-[18F]fluoro-2-deoxy-d-glucose ([18F]FDG) and the role of ethanol, radioactive concentration and temperature of storage

Dantas, Narayanna M.; Nascimento, José William Araújo do; Santos-Magalhães, Nereide Stela; Oliveira, Marcus Aurélio Taborda de

doi:10.1016/j.apradiso.2012.10.017

Cited by 8 publications

(7 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It was reported that the presence of ethanol reduces the radiolysis of radioactive compounds [20–22]; therefore, our diluent was formulated to contain 1% ethanol. Using this formulation, the product was found to be stable at ambient temperature for up to 6 h. Fig.…”

Section: Resultsmentioning

confidence: 99%

Optimization of precursor synthesis, formulation and stability of 1′-[18F]fluoroethyl-β-D-lactose ([18F]FEL) for preclinical studies in detection of pancreatic cancer

Paolillo¹,

Palatis²,

Alauddin³

2014

Nuclear Medicine and Biology

View full text Add to dashboard Cite

Introduction 1′-[18 F]Fluoroethyl-β-d-lactose ([18 F]FEL) is a new PET imaging agent for early detection of pancreatic cancer and hepatocellular carcinoma. We previously reported the syntheses of [18 F]FEL using a bromo- and a tosyl- precursor, followed by an improved method using a nosyl-precursor. However, some steps in the synthesis of the precursor appeared to be problematic producing low yields. Here, we report on an optimized method for synthesis of the precursor and production of [18 F]FEL; we also describe [18 F]FEL’s formulation and stability. Methods Acetylation of d-lactose 1 was performed following a literature procedure to obtain 1′,2′,3′,6′,2,3,4,6-d-lactose octa-acetate 2a/2b. Bromination of 2a/2b was performed using HBr/acetic acid to produce 1'-bromo-2′,3′,6′,2,3,4,6-hepta-O-acetyl-α-d-lactose 3. Coupling of 3 with ethylene glycol was performed in the presence of Ag-tosylate and an excess of ethylene glycol to produce 4a. Compound 4a was reacted with p-nitrophenylsulfonyl chloride to produce the nosyl derivative 5. Radiofluorination of 5 was performed using K[18 F]fluoride/kryptofix to obtain 6, which was purified by HPLC and hydrolyzed with Na-methoxide to produce 7. Results Compound 2 (2a/2b) was obtained in 83% yield as a mixture of two anomeric products. Compound 3 was obtained from the 2a/2b mixture in 80% yield as one product. Coupling of 3 with ethylene glycol produced 4a in 90% yield. Compound 5 was obtained in 64% yield, and radiofluorination of 5 produced 6 in 62.5% ± 7.5% yields (n = 8). Hydrolysis of 6 with Na-methoxide produced 7 in 42.0% ± 7.0% yield (n = 8) from the end of bombardment. Conclusions A simple 4-step synthesis of the precursor, compound 5, has been achieved with improved yields. A new formulation of [18 F]FEL has been developed that allows the product to remain stable at ambient temperature for use in animal studies. This improved synthesis of the precursor and stable formulation of [18 F]FEL should be useful for routine production of the radiotracer and its preclinical and, possibly, clinical applications.

show abstract

Section: Resultsmentioning

confidence: 99%

Optimization of precursor synthesis, formulation and stability of 1′-[18F]fluoroethyl-β-D-lactose ([18F]FEL) for preclinical studies in detection of pancreatic cancer

Paolillo¹,

Palatis²,

Alauddin³

2014

Nuclear Medicine and Biology

View full text Add to dashboard Cite

show abstract

“…This contrasts with Jacobson et al ( 2009 ). Similar to Fawdry ( 2007 ) and Jacobson et al ( 2009 ), Dantas et al ( 2013 ) showed that the degradation of [ 18 F]FDG to free [ 18 F - ]fluoride ions increases until approx. 4 h EOS, after which the increase due to radiolysis is offset by the decay of [ 18 F]fluoride and stabilizes at approx.…”

Section: Discussionmentioning

confidence: 63%

“…Ethanol in the concentrations used in the FDG-production has no or very limited conservational effects on microbiota. Dantas et al ( 2013 ) investigated whether sterility was maintained during repeated withdrawal from a multidose vial containing [ 18 F]FDG and found that this practice does not pose a risk to the patient as long as it is performed according to aseptic technique with the right sterile equipment. Furthermore, for our stability studies the activity was set to be 4 GBq/mL at EOS.…”

Section: Discussionmentioning

confidence: 99%

“…The most well-known and frequently used radio-stabilizer is ethanol. Dantas et al ( 2013 ) found that ethanol content of 0.1–0.4% was sufficiently stable hours in terms of radiochemical purity for up to 16. However, no correlation was found between ethanol concentration and radiochemical purity.…”

Section: Discussionmentioning

confidence: 99%

“…Dantas et al ( 2013 ) studied the stability of [ 18 F]FDG at three different temperatures, 5, 25 and 40° C, every two hours for 16 hours. They found that the temperature had no effect on the degradation.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Stability evaluation of [18F]FDG: literature study, stability studies from two different PET centres and future recommendations

Holler¹,

Renmælmo

Fjellaksel

2022

EJNMMI radiopharm. chem.

View full text Add to dashboard Cite

Background The need for a stability evaluation of [18F]FDG is evident. The main purpose of this study was to make recommendations for determining the shelf life based on the available stability literature and our own two-centre stability studies. Results We performed a non-systematic literature study to find the most relevant stability data for [18F]FDG. The amount of radioactivity, radio-stabilizers, choice of synthesis, dilution, pH, temperature, storage and the choice of stability tests and acceptance criteria were the most important factors to evaluate for the implementation of good manufacturing practice. Moreover, we discuss some limitations of the study, especially the choice of synthesis, photostability, the environment, temperature and storage. Based on these data, we designed our own two-centre stability studies. All the defined acceptance criteria were met. Conclusions We have made recommendations for future stability evaluations based on our findings. The most important findings were that the amount of the radio-stabilizer ethanol should be > 0.1 % ethanol for activities up to 4 GBq/mL and > 0.2 % ethanol for activities up to 22.7 GBq/mL to keep [18F]FDG stable.

show abstract

A two‐center study for the quality control of [18F]FDG using FASTlab phosphate cassettes

et al. 2016

View full text Add to dashboard Cite

The US (USP), British (BP), European (EP) and Japanese (JP) pharmacopeias demand that [(18)F]FDG for injection should be clear and particulate free within the given shelf-life/expiration time. To avoid Al-phosphate precipitation within the product expiry time, FASTlab citrate cassettes, rather than phosphate cassettes, should be used for [(18)F]FDG production. Although testing for Al(3+) is not listed in the [(18)F]FDG monographs of the USP, BP and EP, residual Al(3+) levels should be considered in the interests of patient safety.

show abstract

Radiolysis of 2-[18F]fluoro-2-deoxy-d-glucose ([18F]FDG) and the role of ethanol, radioactive concentration and temperature of storage

Cited by 8 publications

References 8 publications

Optimization of precursor synthesis, formulation and stability of 1′-[18F]fluoroethyl-β-D-lactose ([18F]FEL) for preclinical studies in detection of pancreatic cancer

Optimization of precursor synthesis, formulation and stability of 1′-[18F]fluoroethyl-β-D-lactose ([18F]FEL) for preclinical studies in detection of pancreatic cancer

Stability evaluation of [18F]FDG: literature study, stability studies from two different PET centres and future recommendations

A two‐center study for the quality control of [18F]FDG using FASTlab phosphate cassettes

Contact Info

Product

Resources

About