Labeling approaches for the GE11 peptide, an epidermal growth factor receptor biomarker

The epidermal growth factor receptor (EGFR) is involved in the proliferation and differentiation of normal and malignant cells and is a major therapeutic target for a variety of human cancers. The peptide GE11 was reported to bind efficiently to the EGFR. Labeling GE11 with radionuclides may aid in the quantification of EGFR expression in tumors via noninvasive imaging. To this end, a GGGK linker was attached to the peptide (GE11′), which was conjugated with prosthetic‐labeled groups such as [ 18 F] N ‐succinimidyl 4‐fluorobenzoate ([ 18 F]SFB), [ 18 F](2‐{2‐[2‐(2‐fluoro‐ethoxy)‐ethoxy]‐ethoxy}‐ethoxy)‐propyne ([ 18 F]F‐PEG4‐propyne), [ 124 I] N ‐succinimidyl 4‐iodobenzoate, and the NOTA‐Bn‐NCS chelator for 111 In labeling. All labeled analogs were successfully prepared with radiochemical purity >95% and were identified by HPLC based on their non‐labeled standards. [ 18 F]SFB and [ 18 F]F‐PEG4‐propyne were obtained with a decay‐corrected yield (DCY) of 26% and 30% and a specific activity (SA) of 844 and 2580 Ci/mmol, respectively. [ 124 I] N ‐Succinimidyl 4‐iodobenzoate was obtained with a DCY of 65% and an SA of 3600 Ci/mmol. The DCYs for [ 18 F]4‐fluoro‐benzoate‐GE11′, [ 18 F]F‐PEG4‐1,3‐triazole‐GE11′, and [ 124 I]4‐iodo‐benzoate‐GE11′ were 8%, 10%, and 30%, and the SAs were 108, 500, and 300 Ci/mmol, respectively. [ 111 In]‐NOTA‐GE11′ was prepared with 60% radiochemical yield (RCY) and a SA of 0.35 Ci/mmol. GE11 was also labeled directly with 124 I, using chloramine‐T, yielding [ 124 I]GE11 with 47% RCY and a SA of 1030 Ci/mmol. Copyright © 2011 John Wiley & Sons, Ltd.