One-step and one-pot-two-step radiosynthesis of cyclo-RGD-(18)F-aryltrifluoroborate conjugates for functional imaging.

Arylboronates capture aqueous (18)F-fluoride in one step to afford a highly polar (18)F-labeled aryltrifluoroborate anion ((18)F-ArBF(3) (-)) that clears rapidly in vivo. To date however, there is little data to show that a ligand labeled with a prosthetic (18)F-ArBF(3) (-) will provide functional images. RGD, a high-affinity ligand for integrins that are present on the cell surface of numerous tumors, has been labeled in many formats with many different radionuclides, and as such represents a well-established ligand that can be used to evaluate new labeling methods. Herein we have labeled RGD with a prosthetic (18)F-ArBF(3) (-) via two approaches for the first time: 1) a RGD-boronate bioconjugate is directly labeled in one step and 2) an alkyne-modified arylborimidine is first converted to the corresponding (18)F-ArBF(3) (-) which is then conjugated to an RGD-azide via Cu(+)-mediated [2+3] dipolar cycloaddition in one pot over two steps. RGD-(18)F-ArBF(3) (-) bionconjugates were produced in reasonable radiochemical yields using low amounts of (18)F-fluoride anion (10-50 mCi). Despite relatively low specific activities, good tumor images are revealed in each case.