Facile synthesis and18F-radiolabeling of α4β1-specific LLP2A-aryltrifluoroborate peptidomimetic conjugates.
The peptidomimetic, LLP2A, is a specific, high-affinity ligand for α4β1integrin receptors. Previously, several PEGylated LLP2A conjugates were evaluated in vivo as imaging agents for the detection of lymphoma, leukemia, multiple myeloma and melanoma tumours via NIR-fluorescence,111In-SPECT, and64Cu- and68Ga-PET imaging. Despite these successes, to date there is no report of an18F-labeled LLP2A conjugate. Notably, fluorine-18 is a preferred radionuclide for PET imaging, yet its short half-life and general inactivity under aqueous conditions present challenges for peptide labeling. A simple method for labeling complex biomolecules can be achieved with arylboronic acids that readily capture aqueous [18F]-fluoride ion resulting in an18F-labeled aryltrifluoroborate ([18F]-ArBF3-) radioprosthetic group. Herein, we present the first radiosynthesis of an18F-labeled LLP2A conjugate by both one-step18F-labeling and one-pot two-step18F-labeling post-'click' conjugation of the18F-alkynyl-ArBF3-prosthetic. Competition with a fluorescent conjugate of LLP2A demonstrated specific binding of the non-radioactive isotopolog ArBF3--PEG2-LLP2A to α4β1integrin-expressing MOLT-4 leukemia cells, as evidenced and confirmed by fluorescence microscopy. This work provides a key first step in the development of an expanding library of [18F]-R-BF3--LLP2A radiotracers for PET imaging.
Chemistry Department, University of British Columbia, 2036 Main Mall, Vancouver, British Columbia V6T 1Z1, Canada.
Daniel
D
Walker
Chemistry Department, University of British Columbia, 2036 Main Mall, Vancouver, British Columbia V6T 1Z1, Canada.
Ying
Y
Li
Chemistry Department, University of British Columbia, 2036 Main Mall, Vancouver, British Columbia V6T 1Z1, Canada.
Áron
Á
Roxin
Triumf, 4004 Wesbrook Mall, Vancouver, BC V6T 2A3, Canada.
Paul
P
Schaffer
Triumf, 4004 Wesbrook Mall, Vancouver, BC V6T 2A3, Canada.
Michael J
MJ
Adam
Chemistry Department, University of British Columbia, 2036 Main Mall, Vancouver, British Columbia V6T 1Z1, Canada. Electronic address: dperrin@chem.ubc.ca.
David M
DM
Perrin
D005462:Fluorine Radioisotopes / Q000378:metabolism*; D039041:Integrin alpha4beta1 / Q000378:metabolism*; D057786:Peptidomimetics; D049268:Positron-Emission Tomography
D005462:Fluorine Radioisotopes; D039041:Integrin alpha4beta1; D057786:Peptidomimetics
F-18; Integrin receptor; Peptidomimetic; Radiotracer