scholarly journals Late‐Stage 18 F‐Difluoromethyl Labeling of N‐Heteroaromatics with High Molar Activity for PET Imaging

2019 ◽  
Vol 131 (37) ◽  
pp. 13283-13288 ◽  
Author(s):  
Laura Trump ◽  
Agostinho Lemos ◽  
Bénédicte Lallemand ◽  
Patrick Pasau ◽  
Joël Mercier ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Late Stage ◽  
Molar Activity

scholarly journals Late‐Stage 18 F‐Difluoromethyl Labeling of N‐Heteroaromatics with High Molar Activity for PET Imaging

2019 ◽  
Vol 58 (37) ◽  
pp. 13149-13154 ◽  
Author(s):  
Laura Trump ◽  
Agostinho Lemos ◽  
Bénédicte Lallemand ◽  
Patrick Pasau ◽  
Joël Mercier ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Late Stage ◽  
Molar Activity

scholarly journals Novel late-stage radiosynthesis of 5-[18F]-trifluoromethyl-1,2,4-oxadiazole (TFMO) containing molecules for PET imaging

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nashaat Turkman ◽  
Daxing Liu ◽  
Isabella Pirola
Keyword(s):  
Late Stage ◽  
Histone Deacetylases ◽  
Radiochemical Purity ◽  
Radiochemical Yield ◽  
Single Step ◽  
The Novel ◽  
Molar Activity ◽  
The Central Nervous System ◽  
Class Iia Hdacs ◽  
18F Fluoride

AbstractSmall molecules that contain the (TFMO) moiety were reported to specifically inhibit the class-IIa histone deacetylases (HDACs), an important target in cancer and the disorders of the central nervous system (CNS). However, radiolabeling methods to incorporate the [18F]fluoride into the TFMO moiety are lacking. Herein, we report a novel late-stage incorporation of [18F]fluoride into the TFMO moiety in a single radiochemical step. In this approach the bromodifluoromethyl-1,2,4-oxadiazole was converted into [18F]TFMO via no-carrier-added bromine-[18F]fluoride exchange in a single step, thus producing the PET tracers with acceptable radiochemical yield (3–5%), high radiochemical purity (> 98%) and moderate molar activity of 0.33–0.49 GBq/umol (8.9–13.4 mCi/umol). We validated the utility of the novel radiochemical design by the radiosynthesis of [18F]TMP195, which is a known TFMO containing potent inhibitor of class-IIa HDACs.

scholarly journals 2-Nitroimidazole-Furanoside Derivatives for Hypoxia Imaging—Investigation of Nucleoside Transporter Interaction, 18F-Labeling and Preclinical PET Imaging

2019 ◽  
Vol 12 (1) ◽  
pp. 31
Author(s):  
Florian Maier ◽  
Anna Schweifer ◽  
Vijaya Damaraju ◽  
Carol Cass ◽  
Gregory Bowden ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Tumor Hypoxia ◽  
Radiochemical Yield ◽  
Nucleoside Transporters ◽  
Nucleoside Transporter ◽  
Hypoxia Imaging ◽  
Molar Activity ◽  
Slow Kinetics ◽  
Sugar Derivatives

The benefits of PET imaging of tumor hypoxia in patient management 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 α-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.

scholarly journals A Fluoride-Derived Electrophilic Late-Stage Fluorination Reagent for PET Imaging

Science ◽  
2011 ◽  
Vol 334 (6056) ◽  
pp. 639-642 ◽  
Author(s):  
E. Lee ◽  
A. S. Kamlet ◽  
D. C. Powers ◽  
C. N. Neumann ◽  
G. B. Boursalian ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Late Stage

scholarly journals Increasing molar activity by HPLC purification improves 68Ga-DOTA-NAPamide tumor accumulation in a B16/F1 melanoma xenograft model

2019 ◽  
Author(s):  
Jan Lennart von Hacht ◽  
Sarah Erdmann ◽  
Lars Niederstadt ◽  
Sonal Prasad ◽  
Asja Wagener ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Xenograft Model ◽  
Positron Emission Tomography Imaging ◽  
Peptide Receptor Radionuclide Therapy ◽  
Melanocortin Receptor ◽  
Target Tissue ◽  
Tumor Uptake ◽  
Molar Activity ◽  
Biodistribution Studies ◽  
Unlabeled Peptide

AbstractPurposeMelanocortin receptor 1 is overexpressed in melanoma and may be a molecular target for imaging and peptide receptor radionuclide therapy. 68Gallium labeling of DOTA-conjugated peptides is an established procedure in the clinic for use in positron emission tomography imaging. Aim of this study was to compare a standard labeling protocol against the 68Ga-DOTA peptide purified from the excess of unlabeled peptide.ProceduresThe MC1R ligand DOTA-NAPamide was labeled with 68Ga using a standard clinical protocol. Radioactive peptide was separated from the excess of unlabeled DOTA-NAPamide by HPLC. Immediately after the incubation of peptide and 68Ga (95 °C, 15 min), the reaction was loaded on a C18 column and separated by a water/acetonitrile gradient, allowing fractionation in less than 20 minutes. Radiolabeled products were compared in biodistribution studies and PET imaging using nude mice bearing MC1R-expressing B16/F1 xenograft tumors.ResultsIn biodistribution studies, the non-purified 68Ga-DOTA-NAPamide did not show significant uptake in the tumor at 1 h post injection (0.78% IA/g). By the additional HPLC step, the molar activity was raised around 10,000-fold by completely removing unlabeled peptide. Application of this rapid purification strategy led to a more than 8-fold increase in tumor uptake (7.0% IA/g). The addition of various amounts of unlabeled DOTA-NAPamide to the purified product led to a blocking effect and a decreased specific tumor uptake, similar to the result seen with non-purified radiopeptide. PET imaging was performed using the same tracers for biodistribution. Purified 68Ga-DOTA-NAPamide, in comparison, showed superior tumor uptake.ConclusionsWe demonstrated that chromatographic separation of radiolabeled from excess unlabeled peptide is technically feasible and beneficial, even for short-lived isotopes such as 68Ga. Unlabeled peptide molecules compete with receptor binding sites in the target tissue. Purification of the radiopeptide therefore improved tumor uptake.

Green approaches to late-stage fluorination: radiosyntheses of 18F-labelled radiopharmaceuticals in ethanol and water

2015 ◽  
Vol 51 (79) ◽  
pp. 14805-14808 ◽  
Author(s):  
Megan N. Stewart ◽  
Brian G. Hockley ◽  
Peter J. H. Scott
Keyword(s):  
Pet Imaging ◽  
Late Stage

Green strategies for late-stage fluorination with 18F, in which ethanol and water are the only solvents used throughout the entire radiolabeling process, have been developed and applied to the radiosyntheses of a range of radiopharmaceuticals commonly employed in clinical PET imaging.

scholarly journals Rapid Aqueous Late‐Stage Radiolabelling of [GaF 3 (BnMe 2 ‐tacn)] by 18 F/ 19 F Isotopic Exchange: Towards New PET Imaging Probes

2018 ◽  
Vol 57 (22) ◽  
pp. 6658-6661 ◽  
Author(s):  
Francesco M. Monzittu ◽  
Imtiaz Khan ◽  
William Levason ◽  
Sajinder K. Luthra ◽  
Graeme McRobbie ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Late Stage ◽  
Isotopic Exchange ◽  
Imaging Probes

Late Stage Benzylic C–H Fluorination with [18F]Fluoride for PET Imaging

2014 ◽  
Vol 136 (19) ◽  
pp. 6842-6845 ◽  
Author(s):  
Xiongyi Huang ◽  
Wei Liu ◽  
Hong Ren ◽  
Ramesh Neelamegam ◽  
Jacob M. Hooker ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Late Stage ◽  
18F Fluoride

scholarly journals A high molar activity 18F-labeled TAK-875 derivative for PET imaging of pancreatic β-cells

2018 ◽  
Vol 3 (1) ◽  
Author(s):  
Mark H. Dornan ◽  
Daniil Petrenyov ◽  
José-Mathieu Simard ◽  
Antonio Aliaga ◽  
Guoming Xiong ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Molar Activity

scholarly journals Synthesis and Initial In Vivo Evaluation of [11C]AZ683—A Novel PET Radiotracer for Colony Stimulating Factor 1 Receptor (CSF1R)

2018 ◽  
Vol 11 (4) ◽  
pp. 136 ◽  
Author(s):  
Sean Tanzey ◽  
Xia Shao ◽  
Jenelle Stauff ◽  
Janna Arteaga ◽  
Phillip Sherman ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Radiochemical Purity ◽  
Colony Stimulating Factor ◽  
In Vivo Evaluation ◽  
Molar Activity ◽  
Positron Emission ◽  
New Strategy ◽  
Activity Yield ◽  
Stimulating Factor

Positron emission tomography (PET) imaging of Colony Stimulating Factor 1 Receptor (CSF1R) is a new strategy for quantifying both neuroinflammation and inflammation in the periphery since CSF1R is expressed on microglia and macrophages. AZ683 has high affinity for CSF1R (Ki = 8 nM; IC50 = 6 nM) and >250-fold selectivity over 95 other kinases. In this paper, we report the radiosynthesis of [11C]AZ683 and initial evaluation of its use in CSF1R PET. [11C]AZ683 was synthesized by 11C-methylation of the desmethyl precursor with [11C]MeOTf in 3.0% non-corrected activity yield (based upon [11C]MeOTf), >99% radiochemical purity and high molar activity. Preliminary PET imaging with [11C]AZ683 revealed low brain uptake in rodents and nonhuman primates, suggesting that imaging neuroinflammation could be challenging but that the radiopharmaceutical could still be useful for peripheral imaging of inflammation.

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