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F-18 Labeling Protocol of Peptides Based on Chemically Orthogonal Strain-Promoted Cycloaddition under Physiologically Friendly Reaction Conditions

2012; American Chemical Society; Volume: 23; Issue: 8 Linguagem: Inglês

10.1021/bc3002425

1520-4812

Kalme Sachin, Vinod H. Jadhav, Eun‐Mi Kim, Hye Lan Kim, Sang Bong Lee, Hwan‐Jeong Jeong, Seok Tae Lim, Myung‐Hee Sohn, Dong Wook Kim,

Chemical Synthesis and Analysis

We introduce the high-throughput synthesis of various 18F-labeled peptide tracers by a straightforward 18F-labeling protocol based on a chemo-orthogonal strain-promoted alkyne azide cycloaddition (SPAAC) using aza-dibenzocyclootyne-substituted peptides as precursors with 18F-azide synthon to develop peptide based positron emission tomography (PET) molecular imaging probes. The SPAAC reaction and subsequent chemo-orthogonal purification reaction with azide resin proceeded quickly and selectively under physiologically friendly reaction conditions (i.e., toxic chemical reagents-free, aqueous medium, room temperature, and pH ≈7), and provided four 18F-labeled tumor targetable bioactive peptides such as cyclic Arg-Gly-Asp (cRGD) peptide, bombesin (BBN), c-Met binding peptide (cMBP), and apoptosis targeting peptide (ApoPep) in high radiochemical yields as direct injectable solutions without any HPLC purification and/or formulation processes. In vitro binding assay and in vivo PET molecular imaging study using the 18F-labeled cRGD peptide also demonstrated a successful application of our 18F-labeling protocol.