Evaluation of 4-[18F]fluorobenzoyl-FALGEA-NH2 as a positron emission tomography tracer for epidermal growth factor receptor mutation variant III imaging in cancer

Site‐Selective, Late‐Stage C−H 18F‐Fluorination on Unprotected Peptides for Positron Emission Tomography Imaging

“…The EGFRvIII‐targeting peptide FALGEA‐NH 2 was also directly radiofluorinated providing [ 18 F]FAfLGEA‐NH 2 ( 31 ) (RCC ≈10 %) after ≈80 min total radiosynthesis time. This last result compares well to previous labelling studies of FALGEA‐NH 2 that involved coupling with the [ 18 F]fluorobenzoic acid ([ 18 F]FBA) prosthetic group and proceeded with RCYs ranging from of 2.6–9.8 % (decay corrected) after a 3 h radiosynthesis . Finally, the NAAG peptidase inhibitor ZJ‐43 was directly fluorinated to provide 32 , and fluorination of a homologated analogue afforded the 18 F‐labelled peptide 33 .…”

In vivoevaluation of EGFRvIII mutation in primary glioblastoma patients via complex multiparametric MRI signature

“…Importantly, our results indicated that heterogeneity in both imaging signals and spatial tumor distribution correlates with the mutation's presence. Although molecular imaging ligands under development for PET 31,32 and other molecular imaging modalities aim to more directly evaluate the presence of mutations, these methods are limited by the need to (i) develop specialized ligands for each target mutation and (ii) have multiple scans for evaluating multiple mutations. Our radiomic signature is derived from routine clinically acquired mpMRI, and therefore is easily translatable to the clinic.…”

Site‐Selective, Late‐Stage C−H 18F‐Fluorination on Unprotected Peptides for Positron Emission Tomography Imaging

“…TheEGFRvIII-targeting peptide FALGEA-NH 2 [30] was also directly radiofluorinated providing [ 18 F]FAfLGEA-NH 2 (31)( RCC % 10 %) after % 80 min total radiosynthesis time.This last result compares well to previous labelling studies of FALGEA-NH 2 that involved coupling with the [ 18 F]fluorobenzoic acid ([ 18 F]FBA) prosthetic group and proceeded with RCYs ranging from of 2.6-9.8 %( decay corrected) after a3hr adiosynthesis. [34] Finally,t he NAAG peptidase inhibitor ZJ-43 [32] was directly fluorinated to provide 32,a nd fluorination of ah omologated analogue afforded the 18 F-labelled peptide 33.W en ote that these are the only examples of prostethic group free 18 F-fluorination within this important family of prostate cancer imaging agents. [35] Importantly,a nalysis of the biodistribution of [ 18 F]ZJ-43 (32)i nh ealthy mice showed low bone accumulation (1.7 %I Dg À1 )s uggesting that the peptidic [ 18 F]fluoroleucine fragment is not susceptible to the same degradation pathways of [ 18 F]fluoroleucine itself,w hich displays significant bone accumulation (11.9 %I Dg À1 ).…”