An Organotrifluoroborate for Broadly Applicable One‐Step ¹⁸F‐Labeling

Abstract

A new zwitterionic organotrifluoroborate is appended to three radiosynthons that afford undergo facile bioconjugation to several clinically relevant peptides and one enzyme inhibitor. Molecularly complex bioconjugates are (18)F-labeled in a single aqueous step in rapid time (<15 min) without HPLC purification to afford tracers in good yields (>200 mCi, 20-40%) at high specific activity (≥3 Ci/μmol) and at >98% purity. PET imaging shows in vivo stability and tumor uptake.

18F-AmBF3-MJ9: A novel radiofluorinated bombesin derivative for prostate cancer imaging

“…29 In this study, we introduced a novel GRPR-targeting peptide 18 FAmBF 3 -MJ9 for PET imaging of prostate cancer. AmBF 3 -MJ9 was designed for labeling via the 18 F-19 F isotope exchange reaction on AmBF 3 recently reported by Perrin et al 23,31 The AmBF 3 -conjugated alkyne 2 was coupled to an RM26 derivative, azidoacetyl-MJ9, via Cu-catalyzed 2+3 dipolar cycloaddition to yield AmBF 3 -MJ9. The affinity of the parent peptide (H-D-Phe-Gln-Trp-Ala-Val-Gly-His-(3S,4S)AHMHA-Leu-NH 2 ) was measured in rat pancreatic acini by Llinares et al, and found to be 0.9 nM.…”

“…23 All other chemicals and solvents were obtained from commercial sources, and used without further purification. [ 125 I-Tyr 4 ]-Bombesin (81.4 TBq/mmol) was purchased from Perkin Elmer (Waltham, MA).…”

“…Previously we reported a facile one-step 18 F-labeling approach via 18 F- 19 F isotope exchange reaction on an ammoniomethyltrifluoroborate (AmBF 3 ) moiety 23 generality of this approach for the design of peptide-based 18 Flabeled tracers, we report the synthesis and biological evaluation of a novel GRPR antagonist 18 F-AmBF 3 -MJ9 (Scheme 1) for prostate cancer imaging.…”

One-step 18F labeling of biomolecules using organotrifluoroborates

“…These laborious procedures, such as azeotropic drying and HPLC purification, often reduce the radiochemical yield, while at the same time they increase the risk of synthetic failure. To solve these problems, a one-step and easy-to-follow protocol is described here for peptide radiolabeling that is based on the use of a recently developed organotrifluoroborate 18 .…”

One-step synthesis of an 18F-labeled boron-derived methionine analog: a substitute for 11C-methionine?

“…Based on in vitro assays, the uptake of 18 F-BAA is mediated by various amino acid transporters and they are kinetically indistinguishable from natural amino acids, and hence they truly mirror the uptake behavior of natural amino acids, although they are not incorporated into proteins. With this strategy of amino acid mimicry, in addition to t h e o n e -s t e p 1 8 F -l a b e l i n g m e t h o d u t i l i z i n g a n organotrifluoroborate which was also developed by the same investigators [16,17], the BAAs may serve as general PET imaging probes for amino acid transporters. All amino acids can be radiolabeled in a similar fashion for imaging amino acid transporter activity and tumor metabolism, which could complement the use of 18 F-FDG in the imaging of tumor types in which 18 F-FDG does not work well (e.g.…”