Evaluation of an integrin αvβ6-specific peptide labeled with [18F]fluorine by copper-free, strain-promoted click chemistry

Sven H. Hausner, Richard D. Carpenter, Nadine Bauer, Julie Sutcliffe

Research output: Contribution to journalArticlepeer-review

41 Scopus citations


Introduction: Click chemistry, particularly the Huisgen 1,3-dipolar cycloaddition of an alkyne with an azide, has quickly become popular for site-specific radiolabeling. Recently, strain-promoted click chemistries have been developed, eliminating the need for potentially toxic copper catalysts. This study presents radiolabeling of an αvβ6 integrin targeting peptide (A20FMDV2) via strain-promoted click using a fluorine-18 prosthetic group, and in vitro and in vivo evaluation. Methods: The radiotracer [18F]FBA-C6-ADIBON3-PEG7-A20FMDV2 (1) was prepared from [18F]FBA-C6-ADIBO (2) and N3-PEG7-A20FMDV2 (ethanol; 10min; 35-45°C). HPLC-purified and formulated radiotracer 1 was evaluated in vitro by cell binding (DX3puroβ6, αvβ6-positive; and DX3puro, αvβ6-negative control) and serum stability, and in vivo using PET/CT imaging and biodistribution studies in mice. Results: The radiotracer 1 was readily prepared and purified (from 2: 40±4min including HPLC, 11.9±3.2% decay corrected isolated radiochemical yield, >99% radiochemical purity, n=4) and displayed good stability (1h: >99%, saline; 94.6%, serum). Strong αvβ6-targeted binding was observed in vitro (DX3puroβ6 cells, 15min: 43.2% binding, >6:1 for DX3puroβ6:DX3puro). In the mouse model DX3puroβ6-tumor binding was low (1h: 0.47±0.28% ID/g, 4h: 0.14±0.09% ID/g) and clearing from the bloodstream was via the renal and hepatobiliary routes (urine: 167±84% ID/g at 1h, 10.3±4.8% ID/g at 4h; gall bladder: 95±33% ID/g at 1h, 63±11% ID/g at 4h). Conclusion: Copper-free, strain-promoted click chemistry is an attractive, straightforward approach to radiolabeling. Although the [18F]FBA-C6-ADBIO-based prosthetic group did not interfere with αvβ6-targeted binding in vitro, it did influence the pharmacokinetics, possibly due to its size and lipophilic nature.

Original languageEnglish (US)
Pages (from-to)233-239
Number of pages7
JournalNuclear Medicine and Biology
Issue number2
StatePublished - Feb 2013


  • Copper-free
  • Cyclooctyne
  • Diagnostic radionuclides
  • Fluorine 18
  • Positron
  • Strain-promoted click

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Medicine
  • Radiology Nuclear Medicine and imaging


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