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Chemical Structure| 403-45-2 Chemical Structure| 403-45-2
Chemical Structure| 403-45-2

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Product Citations

Kanellopoulos, Panagiotis ; Lundmark, Fanny ; Abouzayed, Ayman ; Balestri, Lorenzo Jacopo Ilic ; Håkansson, Esther Olaniran ; Obeid, Karim , et al.

Abstract: Background: The gastrin-releasing peptide receptor (GRPR) is overexpressed in the majority of primary prostate cancer lesions, with persistent expression in lymph nodes and bone metastases, making it a legitimate molecular target for diagnostic imaging and staging. This study presents the synthesis and preclinical evaluation of [18F]MeTz-PEG2-RM26, a GRPR antagonist which utilises the Inverse Electron Demand Diels-Alder (IEDDA) reaction for 18F-labelling. This click-chemistry approach allows for site-specific incorporation of fluorine-18 under mild conditions, preserving the peptide's structural integrity and biological activity. Receptor specificity and affinity of [18F]MeTz-PEG2-RM26 were evaluated in vitro using GRPR-expressing PC-3 cells. Furthermore, the biodistribution profile of [18F]MeTz-PEG2-RM26 was assessed in NMRI mice and its tumour-targeting capability was investigated in mice bearing PC-3 xenografts. Results: The labelling of TCO-PEG2-RM26 precursor involved three steps: (1) synthesis of an 18F-labelled activated ester on a quaternary methyl ammonium (QMA) cartridge, (2) conjugation of the labelled ester to a tetrazine amine, and (3) attachment to TCO-PEG2-RM26 via an IEDDA click reaction. This production method of [18F] MeTz-PEG2-RM26 afforded a high apparent molar activity of 3.5–4.3 GBq/µmol and radiochemical purity exceeding 98%, with 43–70 MBq activity incorporation, while the entire synthesis was completed within 75 min. Both in vitro and in vivo studies confirmed the specific binding of [18F]MeTz-PEG2-RM26 to GRPR, with a significant reduction in activity uptake observed upon receptor saturation. The radioligand exhibited rapid blood clearance and minimal bone uptake, confirming the stability of the fluorine-carbon bond. However, high hepatic uptake (12–13% IA/g at 1 h postinjection) indicated predominant hepatobiliary excretion. Receptor-mediated uptake was observed in the tumours and pancreatic tissue, although the overall activity uptake in tumours was low, likely due to the rapid hepatobiliary clearance of [18F] MeTz-PEG2-RM26. Conclusions: These findings demonstrate the effectiveness of the IEDDA click reaction for fluorine-18 labelling of GRPR-targeting PET tracers. Future studies should focus on increasing the hydrophilicity of the imaging probe to improve the targeting properties and biodistribution profile of the radioligand.

Keywords: Fluorine-18 ; TCO ; Tetrazine ; IEDDA click chemistry ; GRPR ; Bombesin ; PET ; Prostate cancer

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Product Details of 6-Fluoronicotinic acid

CAS No. :403-45-2
Formula : C6H4FNO2
M.W : 141.10
SMILES Code : C1=NC(=CC=C1C(=O)O)F
MDL No. :MFCD01859863

Safety of 6-Fluoronicotinic acid

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Application In Synthesis of 6-Fluoronicotinic acid

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 403-45-2 ]

[ 403-45-2 ] Synthesis Path-Downstream   1~3

  • 1
  • [ 403-45-2 ]
  • [ 36805-97-7 ]
  • [ 676560-01-3 ]
  • 2
  • [ 403-45-2 ]
  • [ 75-65-0 ]
  • [ 676560-01-3 ]
YieldReaction ConditionsOperation in experiment
With N,N-dimethylformamide di-tert-butyl acetal; for 3.0h;Heating / reflux; To a stirred and refluxed solution of 6-fluoro-nicotinic acid (0.092 g, 6.52 mmol) in benzene and 2-methyl-propan-2-ol (2: 1,15 : 7 mL) was added dropwise N, N- [DIMETHYLFORMAMIDE] di-tert-butyl acetal (8.2 mL, 29.6 mmol). The reaction mixture was refluxed for 3 hours, cooled to room temperature and partitioned between aqueous [NAHC03] and dichloromethane. The organic layer was washed with water and brine, dried [(MGS04),] filtered, concentrated under reduced pressure and purified by flash chromatography with 15% to 30% ethyl acetate in hexane to provide the titled compound. MS (CI) m/z 197 (M+1) [+] [; IH] NMR (300 MHz, CDC13) [5] ppm 8.82 (d, 1H), 8.38 (m, 1H), 6.98 (d, [1H),] 1.64 (s, 9H).
  • 3
  • [ 403-45-2 ]
  • [ 75-65-0 ]
  • [ 36805-97-7 ]
  • [ 676560-01-3 ]
YieldReaction ConditionsOperation in experiment
In hexane; benzene; Example 40A 6-Fluoro-nicotinic acid tert-butyl ester To a stirred and refluxed solution of 6-fluoro-nicotinic acid (0.092 g, 6.52 mmol) in benzene and 2-methyl-propan-2-ol (2:1, 15:7 mL) was added dropwise N,N-dimethylformamide di-tert-butyl acetal (8.2 mL, 29.6 mmol). The reaction mixture was refluxed for 3 hours, cooled to room temperature and partitioned between aqueous NaHCO3 and dichloromethane. The organic layer was washed with water and brine, dried (MgSO4), filtered, concentrated under reduced pressure and purified by flash chromatography with 15% to 30% ethyl acetate in hexane to provide the titled compound. MS (CI) m/z 197 (M+1)+; 1H NMR (300 MHz, CDCl3) delta ppm 8.82(d, 1H), 8.38(m, 1H), 6.98(d, 1H), 1.64 (s, 9H).
 

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