Nucleophilic ring-opening of activated aziridines: A one-step method for labeling biomolecules with fluorine-18

Roehn, Ulrike; Becaud, Jessica; Mu, Linjing; Srinivasan, Ananth; Stellfeld, Timo; Fitzner, Ansgar; Graham, Keith; Dinkelborg, Ludger; Schubiger, August P.; Ametamey, Simon M.

doi:10.1016/j.jfluchem.2009.07.003

Cited by 38 publications

(28 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Schirrmacher et al reported the direct radiolabeling of an organosilicon-modified peptide in an isotope exchange reaction (32). Several 1-step approaches for the facile 18 F labeling of peptides have been developed in our laboratories (19,31,33). In the present study, 18 F labeling of BAY 86-4367 was achieved in a single step via aromatic nucleophilic substitution.…”

Section: In Vivo Characterizationmentioning

confidence: 80%

“…The distribution coefficient of the nonradioactive 19 F-bombesin derivative (1b) was lower than 23.9. The direct labeling of peptides with 18 F in a single step was recently described by various groups (19,(31)(32)(33). Schirrmacher et al reported the direct radiolabeling of an organosilicon-modified peptide in an isotope exchange reaction (32).…”

Section: In Vivo Characterizationmentioning

confidence: 99%

See 1 more Smart Citation

¹⁸F-Labeled Bombesin Analog for Specific and Effective Targeting of Prostate Tumors Expressing Gastrin-Releasing Peptide Receptors

Honer¹,

Mu²,

Stellfeld³

et al. 2011

J Nucl Med

Self Cite

View full text Add to dashboard Cite

Bombesin is a peptide exhibiting high affinity for the gastrinreleasing peptide receptor (GRPr), which is highly overexpressed on prostate cancer cells. In the present study, we developed an 18 F-labeled bombesin analog, 18 F-BAY 86-4367, which is currently being clinically tested for use in PET of prostate cancer. Methods: In vitro pharmacologic studies were performed to characterize the nonradioactive ( 19 F) standard of the bombesin analog for binding affinity and selectivity for GRPr. The stability of 18 F-BAY 86-4367 was determined in murine and human plasma. In vivo, the tumor-targeting potential and pharmacokinetic profile of the 18 F tracer were analyzed with biodistribution experiments and PET studies of prostate tumor-bearing mice. Results: The nonradioactive ( 19 F) standard of the bombesin analog showed subnanomolar and GRPr-selective binding affinity. The stability of the tracer in murine and human plasma was found to be high. In 2 prostate cancer xenograft models (PC-3 and LNCaP), 18 F-BAY 86-4367 showed more specific and effective GRPr-based targeting in vivo than the benchmark radiotracers 18 F-fluoroethylcholine and 18 F-FDG. In addition, rapid tumor targeting and fast renal excretion (;70%) and hepatobiliary excretion (;10%) were identified in both xenograft models. Furthermore, PET studies provided clear and specific visualization of PC-3 tumors in mice. Conclusion: Favorable preclinical data showing specific and effective tumor targeting by 18 F-BAY 86-4367 suggest that a clinical trial be undertaken to test its diagnostic utility in PET for prostate carcinoma patients.

show abstract

Section: In Vivo Characterizationmentioning

confidence: 80%

Section: In Vivo Characterizationmentioning

confidence: 99%

¹⁸F-Labeled Bombesin Analog for Specific and Effective Targeting of Prostate Tumors Expressing Gastrin-Releasing Peptide Receptors

Honer¹,

Mu²,

Stellfeld³

et al. 2011

J Nucl Med

Self Cite

View full text Add to dashboard Cite

show abstract

“…3) along with its regiosomer ( 7 ). Nucleophilic ring openings of aziridines by fluorine-18 are rare [44–48] although this could be a feasible route to prepare various fluorine-18 labeled radiopharmacuticals. In 2009 Vasdev et al [47] reported a highly regioselective ring-opening of N -benzyloxycarbonyl- protected 2-methylaziridine by fluorine-18 and noted that the ratio of the two isomers could be controlled by the solvent and by modifying the substituent on the nitrogen.…”

Section: Resultsmentioning

confidence: 99%

Synthesis of ApoSense compound [18F]2-(5-(dimethylamino)naphthalene-1-sulfonamido)-2-(fluoromethyl)butanoic acid ([18F]NST732) by nucleophilic ring opening of an aziridine precursor

Basuli

Shi

et al. 2012

Nuclear Medicine and Biology

View full text Add to dashboard Cite

Introduction The small molecule 2-(5-(dimethylamino)naphthalene-1-sulfonamido)-2-(fluoromethyl)butanoic acid (NST732) is a member of the ApoSense® family of compounds, capable of selective targeting, binding and accumulation within cells undergoing apoptotic cell death. It has application in molecular imaging and blood clotting particularly for monitoring anti-apoptotic drug treatments. We are investigating a fluorine-18 radiolabeled analog of this compound for positron emission tomography studies. Methods We prepared the tosylate precursor methyl 2-(5-(dimethylamino)naphthalene-1-sulfonamido)-2-(tosyloxymethyl)butanoate (4) to synthesize fluorine-18 labeled NST732. Fluorination reaction of the tosylate precursor in 1:1 acetonitrile, dimethylsulfoxide with tetrabutyl ammonium fluoride (TBAF) proceeds through an aziridine intermediate (4A) to afford two regioisomers 2-(5-(dimethylamino)naphthalene-1-sulfonamido)-2-fluorobutanoate (5) and methyl 2-(5-(dimethylamino)naphthalene-1-sulfonamido)-2-(fluoromethyl)butanoate (6). Acid hydrolysis of the fluoromethylbutanoate (6) isomer produced NST732. As the fluorination reaction of the tosylate precursor proceeds through an aziridine intermediate (4A) and the fluorination conceivably could be done directly on the aziridine, we have separately prepared an aziridine precursor (4A). Fluorine-18 labeling of the aziridine precursor (4A) was performed with [18F]tetrabutyl ammonium fluoride to afford the same two regioisomers (5 and 6). The [18F]2-((5-dimethylamino)naphthalene-1-sulfonamido)methyl)-2-fluorobutanoic acid (NST732) was then obtained by the hydrolysis of corresponding [18F]-labeled ester (6) with 6N hydrochloric acid. Results Two regioisomers obtained from the fluorination reaction of aziridine were easily separated by HPLC. The total radiochemical yield was 15 ± 3% (uncorrected, n = 18) from the aziridine precursor, in a 70 min synthesis time with a radiochemical purity > 99%. Conclusion Fluorine-18 labeled aposense coumpound [18F]NST732 is prepared in moderate yield by direct fluorination of an aziridine precursor.

show abstract

“…described a one-step labeling of peptides via ring-opening of activated aziridines by [18 F]fluoride (Figure 2). [13] Effects of different activating groups on the aziridine ring were investigated in this study. 2,4,6-Triisopropylphenylsulfone, as shown in the transformation from 9 to 10 , was identified as the optimal activating group to facilitate regioselective aziridine ring-opening by [18 F]fluoride.…”

Section: Direct Methods For 18f-labeling Of Biomoleculesmentioning

confidence: 99%

¹⁸F‐Labeling of Sensitive Biomolecules for Positron Emission Tomography

Krishnan

Vasdev

et al. 2017

Chemistry A European J

View full text Add to dashboard Cite

Positron emission tomography (PET) imaging study of fluorine-18 labeled biomolecules is an emerging and rapidly growing area for preclinical and clinical research. The present review focuses on recent advances in radiochemical methods for incorporating fluorine-18 into biomolecules via ‘direct’ or ‘indirect’ bioconjugation. Recently developed prosthetic groups and pre-targeting strategies, as well as representative examples in 18F-labeling of biomolecules in PET imaging research studies are highlighted.

show abstract

Nucleophilic ring-opening of activated aziridines: A one-step method for labeling biomolecules with fluorine-18

Cited by 38 publications

References 38 publications

¹⁸F-Labeled Bombesin Analog for Specific and Effective Targeting of Prostate Tumors Expressing Gastrin-Releasing Peptide Receptors

¹⁸F-Labeled Bombesin Analog for Specific and Effective Targeting of Prostate Tumors Expressing Gastrin-Releasing Peptide Receptors

Synthesis of ApoSense compound [18F]2-(5-(dimethylamino)naphthalene-1-sulfonamido)-2-(fluoromethyl)butanoic acid ([18F]NST732) by nucleophilic ring opening of an aziridine precursor

¹⁸F‐Labeling of Sensitive Biomolecules for Positron Emission Tomography

Contact Info

Product

Resources

About

Nucleophilic ring-opening of activated aziridines: A one-step method for labeling biomolecules with fluorine-18

Cited by 38 publications

References 38 publications

18F-Labeled Bombesin Analog for Specific and Effective Targeting of Prostate Tumors Expressing Gastrin-Releasing Peptide Receptors

18F-Labeled Bombesin Analog for Specific and Effective Targeting of Prostate Tumors Expressing Gastrin-Releasing Peptide Receptors

Synthesis of ApoSense compound [18F]2-(5-(dimethylamino)naphthalene-1-sulfonamido)-2-(fluoromethyl)butanoic acid ([18F]NST732) by nucleophilic ring opening of an aziridine precursor

18F‐Labeling of Sensitive Biomolecules for Positron Emission Tomography

Contact Info

Product

Resources

About

¹⁸F-Labeled Bombesin Analog for Specific and Effective Targeting of Prostate Tumors Expressing Gastrin-Releasing Peptide Receptors

¹⁸F-Labeled Bombesin Analog for Specific and Effective Targeting of Prostate Tumors Expressing Gastrin-Releasing Peptide Receptors

¹⁸F‐Labeling of Sensitive Biomolecules for Positron Emission Tomography