Corrigendum: Modular Medical Imaging Agents Based on Azide–Alkyne Huisgen Cycloadditions: Synthesis and Pre‐Clinical Evaluation of 18F‐Labeled PSMA‐Tracers for Prostate Cancer Imaging

Abstract

The published article is lacking ah ighly relevantr eference regarding clickable PSMAligandsw ith alkyne-moiety.H ence,t he authors would like to acknowledge the work by Kelly et al. (2017), who already presented six alkyne-functionalized PSMA binding motifs,t hree triazolyl and three triazolylmethoxy variants with subsequent successful radiolabeling with [ 18 F]fluoro-azide using azido-ethylene synthons. The authors would like to apologize for the oversight. The following is the relevant section of the paper with amendments highlightedi n italics: Results and DiscussionDesign of F-PSMA-MIC01.PSMA is aw ell-characterized target in structure-activity-relationship (SAR) studies. [53] The naturalf unctiono ft his membrane zinc-metallopeptidase is to cleave glutamate from N-acetyl-l-aspartyl-l-glutamate. This antigen has ag lutamate-favoring S1'pocket [54][55][56] and SAR analysis revealed an adaptive, hydrophobic-favoring S1-pocket, createdb ya na rginine patch formed by Arg463, Arg534 and Arg536 that can accommodate av ariety of inhibitors. [57] PSMA-targeting compounds with the Glu-urea-Lys motif bind to the S1-hydrophobic pocket and the S1'-pocket, as well as to the zinc ions. [57] Interestingly,i tw as found that the presence of a1 ,2,3-triazole motif in PSMA inhibitors enablesb inding to an additional arene-bindings ite, whichh as inspired us to use this moiety in developing PSMA-targeting radiotracers with high affinity. [57] For this purpose, we designed am odulars ynthesis approach for PSMA-targeting radiotracers which can potentially be applied to different imaging modalities by adapting the existing Glu-urea-Lys motif [57] so that it is able to undergo the Huisgen [3 + + 2]-cycloaddition. Even further,i n2 017i tw as already shown that clickable PSMA-inhibitors are valuable precursors for potent PET imaging agents. [C, 52] Here, we introduce the radiotracer [ 18 F]PSMA-MIC01 (Figure 2A), which is formed by alkyne-Glu-urea-Lys motif and PET-radionuclide 18 F, spacedf rom the 1,2,3-triazoleb y adiethylene-glycol-linker,which was shown to display the right linker length. [51] Compared to the previously published alkyne-PSMA binding motif, [C] our PSMA-binding motif modifies the lysine of the existing Glu-urea-Lys motif to ab enzamide instead of ap henylurea. Additionally,t he synthonu sedf or the [ 18 F]fluorinations is based on azidodiethylene-glycol instead of the azido-ethylene synthon used by Kelly et al. [C] [c] J.

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