^99mTc-bioorthogonal click chemistry reagent for in vivo pretargeted imaging

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• 作者：Marí ; a Fernanda Garcí ; a^a ; ^{fgmelian@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; Xiuli Zhang^b ; ^c ; ^{zhangxiu@missouri.edu" class="auth_mail" title="E-mail the corresponding author} ; Manankumar Shah^b ; ^c ; ^{masvh4@mail.missouri.edu" class="auth_mail" title="E-mail the corresponding author} ; Jessica Newton-Northup^b ; ^c ; ^{newtonj@missouri.edu" class="auth_mail" title="E-mail the corresponding author} ; Pablo Cabral^a ; ^{pabloc7@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; Hugo Cerecetto^a ; ^{hcerecetto@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; Thomas Quinn^b ; ^c ; ^{quinnt@missouri.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：TCO ; trans-cyclooctene ; TZ ; 1 ; 2 ; 4 ; 5-tetrazine ; PET ; Positron Emission Tomography ; HYNIC ; 6-hydrazinonicotinc acid ; SPECT ; Single Photon Emission Computed Tomography ; PBS ; phosphate buffer saline ; BSA ; bovine serum albumin ; ABTS ; 2 ; 2&prime ; -azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) ; RCP ; radiochemical purity ; EDDA ; ethylenediaminediacetic acid ; DMSO ; dimethyl sulfoxide ; SDS&ndash ; PAGE ; sodium dodecyl sulfate polyacrylamide gel electrophoresis ; BSM ; bovine submaxillary glands ; CPM ; counts
• 刊名：Bioorganic & Medicinal Chemistry
• 出版年：2016
• 出版时间：15 March 2016
• 年：2016
• 卷：24
• 期：6
• 页码：1209-1215
• 全文大小：983 K

文摘

Metal-free click chemistry has become an important tool for pretargeted approaches in the molecular imaging field. The application of bioorthogonal click chemistry between a pretargeted trans-cyclooctene (TCO) derivatized monoclonal antibody (mAb) and a ^99mTc-modified 1,2,4,5-tetrazine for tumor imaging was examined in vitro and in vivo. The HYNIC tetrazine compound was synthesized and structurally characterized, confirming its identity. Radiolabeling studies demonstrated that the HYNIC tetrazine was labeled with ^99mTc at an efficiency of >95% and was radiochemically stable. ^99mTc–HYNIC tetrazine reacted with the TCO–CC49 mAb in vitro demonstrating its selective reactivity. In vivo biodistribution studies revealed non-specific liver and GI uptake due to the hydrophobic property of the compound, however pretargeted SPECT imaging studies demonstrated tumor visualization confirming the success of the cycloaddition reaction in vivo. These results demonstrated the potential of ^99mTc–HYNIC–tetrazine for tumor imaging with pretargeted mAbs.