220793-03-3Relevant academic research and scientific papers
Improved synthesis of the hypoxia probe 5-deutero-5-fluoro-5-deoxy-azomycin arabinoside (FAZA) as a model process for tritium radiolabeling
Zanato, Chiara,Testa, Andrea,Zanda, Matteo
, p. 110 - 117 (2013)
Tritium-labelled fluoroazomycin arabinoside, [3H]-FAZA, is a useful probe for the investigation of hypoxia, furthermore it is safer and easier to handle than the PET tracer [18F]-FAZA when used in cell based assays. The only known synthesis of deuterium- and tritium-labelled FAZA was re-investigated and optimized. Then, a new and improved synthesis of [ 2H]-FAZA was developed as a model process for tritium radiolabelling. This novel synthesis is expected to greatly facilitate access to [ 3H]-FAZA.
Fluoroazomycin arabinoside (FAZA): Synthesis, 2H and 3H-labelling and preliminary biological evaluation of a novel 2-nitroimidazole marker of tissue hypoxia
Kumar,Stypinski,Xia,McEwan,Machulla,Wiebe
, p. 3 - 16 (1999)
1-α-D-(5-Fluoro-5-deoxyarabinofuranosyl)-2-nitroimidazole (fluoroazomycin alabinoside; FAZA) 6, a putative PET imaging agent when labelled with 18F, was synthesized by fluorination of 1-α-D-(2,3-di-O-acetylarabinofuranosyl)-2-nitroimidazole with DAST followed by deprotection. The C-5'-deuterated and tritiated analogues were prepared by NaCNBD3 or NaCNBT3 reduction of the protected C-5'-carbonyl intermediate 5, followed by C-5' fluorination and deprotection, to afford C-5' deuterated and C-5' tritiated FAZA, respectively. Preliminary in vivo biodistribution studies in a murine tumour model, and pharmacokinetic studies in rats indicated that 3H-FAZA has biodistribution, tumour uptake and pharmacokinetic properties similar to those of 123I-IAZA, a clinically-proven radiopharmaceutical for SPECT-imaging of hypoxic tissues.
2-nitroimidazole-furanoside derivatives for hypoxia imaging-investigation of nucleoside transporter interaction, 18F-labeling and preclinical PET imaging
Maier, Florian C.,Schweifer, Anna,Damaraju, Vijaya L.,Cass, Carol E.,Bowden, Gregory D.,Ehrlichmann, Walter,Kneilling, Manfred,Pichler, Bernd J.,Hammerschmidt, Friedrich,Reischl, Gerald
, (2019/04/25)
The benefits of PET imaging of tumor hypoxia in patientmanagement has been demonstrated in many examples and with various tracers over the last years. Although, the optimal hypoxia imaging agent has yet to be found, 2-nitroimidazole (azomycin) sugar derivatives-mimicking nucleosides-have proven their potential with [18F]FAZA ([18F]fluoro-azomycin-α-arabinoside) as a prominent representative in clinical use. Still, for all of these tracers, cellular uptake by passive diffusion is postulated with the disadvantage of slow kinetics and low tumor-to-background ratios. We recently evaluated [18F]fluoro-azomycin-β-deoxyriboside (β-[18F]FAZDR), with a structure more similar to nucleosides than [18F]FAZA and possible interaction with nucleoside transporters. For a deeper insight, we comparatively studied the interaction of FAZA, β-FAZA, α-FAZDR and β-FAZDR with nucleoside transporters (SLC29A1/2 and SLC28A1/2/3) in vitro, showing variable interactions of the compounds. The highest interactions being for β-FAZDR (IC50 124 ± 33 μM for SLC28A3), but also for FAZA with the non-nucleosidic a-configuration, the interactions were remarkable (290 ± 44 μM {SLC28A1}; 640 ± 10 μM {SLC28A2}). An improved synthesis was developed for β-FAZA. For a PET study in tumor-bearing mice, α-[18F]FAZDR was synthesized (radiochemical yield: 15.9 ± 9.0% (n = 3), max. 10.3 GBq, molar activity > 50 GBq/μmol) and compared to β-[18F]FAZDR and [18F]FMISO, the hypoxia imaging gold standard. We observed highest tumor-to-muscle ratios (TMR) for β-[18F]FAZDR already at 1 h p.i. (2.52 ± 0.94, n = 4) in comparison to [18F]FMISO (1.37 ± 0.11, n = 5) and α-[18F]FAZDR (1.93 ± 0.39, n = 4), with possible mediation by the involvement of nucleoside transporters. After 3 h p.i., TMR were not significantly different for all 3 tracers (2.5-3.0). Highest clearance from tumor tissue was observed for β-[18F]FAZDR (56.6 ± 6.8%, 2 h p.i.), followed by α-[18F]FAZDR (34.2 ± 7.5%) and [18F]FMISO (11.8 ± 6.5%). In conclusion, both isomers of [18F]FAZDR showed their potential as PET hypoxia tracers. Differences in uptake behavior may be attributed to a potential variable involvement of transport mechanisms.
Novel compounds for hypoxic cell therapy and imaging
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Page/Page column 18, (2010/11/24)
The present invention provides for compounds suitable for therapeutic treatment of hypoxic tissues, particularly for application in radiotherapy, chemosensitization, radiosensitization. The present invention further provides for compounds suitable for rad
NOVEL SUBSTITUTED 2-NITROIMIDAZOLES USEFUL FOR HYPOXIC CELL THERAPY AND IMAGING
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Page/Page column 43, (2010/11/24)
The present invention provides for substituted 2-nitroimidazoles suitable for the therapeutic treatment of hypoxic tissues, particularly for application in radiotherapy, chemosensitization and radiosensitization The present invention further provides subs
