Toward [¹⁸F]-Labeled Aryltrifluoroborate Radiotracers: In Vivo Positron Emission Tomography Imaging of Stable Aryltrifluoroborate Clearance in Mice

Abstract

The use of a boronic ester as a captor of aqueous [(18)F]-fluoride has been previously suggested as a means of labeling biomolecules in one step for positron emission tomography (PET) imaging. For this approach to be seriously considered, the [(18)F]-labeled trifluoroborate should be humorally stable such that it neither leaches free [(18)F]-fluoride to the bone nor accumulates therein. Herein, we have synthesized a biotinylated boronic ester that is converted to the corresponding trifluoroborate salt in the presence of aqueous [(18)F]-fluoride. In keeping with its in vitro aqueous kinetic stability at pH 7.5, the trifluoroborate appears to clear in vivo quite rapidly to the bladder as the stable trifluoroborate salt with no detectable leaching of free [(18)F]-fluoride to the bone. When this labeled biotin is preincubated with avidin, the pharmacokinetic clearance of the resulting complex is visibly altered. This work validates initial claims that boronic esters are potentially useful as readily labeled precursors to [(18)F]-PET reagents.

Novel Matrix Metalloproteinase Inhibitor [18F]Marimastat-Aryltrifluoroborate as a Probe for In vivo Positron Emission Tomography Imaging in Cancer

“…Because three fluoride ions condense with one arylboronate to give an ArBF 3 , the law of mass action ensures that the resulting ArBF 3 has a decay-corrected specific activity that is thrice that of the source fluoride; therefore, activities as high as 30 Ci/μmol may be envisaged if no carrier-added fluoride with a specific activity of 10 Ci/μmol is used. Nevertheless, yields may be low unless reaction volume is minimized; the use of 500 mCi of no carrier-added fluoride with a specific activity of 10 (3,21). Despite a relatively low signal to noise ratio, tumor-labeling was specific as shown from the unlabeled blocking control studies.…”

“…Recently, Ting and colleagues (2) used arylboronate precursors to capture aqueous [ 18 F]fluoride in the form of an aryltrifluoroborate (ArBF 3 ) for 18 F-labeling in a rapid, one-step synthesis under acidic aqueous conditions at room temperature. Indeed, the [ 18 F]aryltrifluoroborate was stable in vivo because no [ 18 F]fluoride accumulation was detected in bone, a highly fluorophilic tissue (3). Such chemistries have the potential to fast-track the introduction of 18 F-labeled bioconjugates in "kit" form 7 for diagnostic imaging in humans.…”

18F-positron-emitting/fluorescent labeled erythrocytes allow imaging of internal hemorrhage in a murine intracranial hemorrhage model

“…These agents are visible by PET, 31,32 are stable in vivo, 33,34 and bear a reactive group for RBCmembrane labeling.…”

Silicon-[18F]Fluorine Radiochemistry: Basics, Applications and Challenges

“…The advent of novel 18 F-labeling methods has just begun. The introduction of Si- 18 F [5][6][7], B- 18 F [5,6] and Al- 18 F [8][9][10][11][12] radiochemistry has set the foundation for the development of novel radiotracers and has the potential to reshape the landscape of 18 F-radiochemistry if some hurdles can be overcome in time. This review article deals primarily with Si- 18 F radiochemistry and the interested reader is advised to further consult various excellent review articles on 18 F-radiochemistry [13][14][15][16][17][18] and original publications about B- 18 F and Al- 18 F chemistry.…”