基于生物正交狄尔斯-阿尔德点击化学的基于氟的预靶向正电子发射断层显像
(18)F-Based Pretargeted PET Imaging Based on Bioorthogonal Diels-Alder Click Chemistry.
作者信息
Meyer Jan-Philip, Houghton Jacob L, Kozlowski Paul, Abdel-Atti Dalya, Reiner Thomas, Pillarsetty Naga Vara Kishore, Scholz Wolfgang W, Zeglis Brian M, Lewis Jason S
机构信息
Department of Radiology, Memorial Sloan Kettering Cancer Center , 1275 York Avenue, New York, New York 10065, United States.
MabVax Therapeutics , 11588 Sorrento Valley Road Suite 20, San Diego, California 92121, United States.
出版信息
Bioconjug Chem. 2016 Feb 17;27(2):298-301. doi: 10.1021/acs.bioconjchem.5b00504. Epub 2015 Oct 28.
A first-of-its-kind (18)F pretargeted PET imaging approach based on the bioorthogonal inverse electron demand Diels-Alder (IEDDA) reaction between tetrazine (Tz) and trans-cyclooctene (TCO) is presented. As proof-of-principle, a TCO-bearing immunoconjugate of the anti-CA19.9 antibody 5B1 and an Al[(18)F]NOTA-labeled tetrazine radioligand were harnessed for the visualization of CA19.9-expressing BxPC3 pancreatic cancer xenografts. Biodistribution and (18)F-PET imaging data clearly demonstrate that this methodology effectively delineates tumor mass with activity concentrations up to 6.4 %ID/g at 4 h after injection of the radioligand.
本文提出了一种基于四嗪（Tz）与反式环辛烯（TCO）之间的生物正交逆电子需求狄尔斯-阿尔德（IEDDA）反应的首创（18）F预靶向PET成像方法。作为原理验证，利用抗CA19.9抗体5B1的携带TCO的免疫缀合物和Al[(18)F]NOTA标记的四嗪放射性配体来可视化表达CA19.9的BxPC3胰腺癌异种移植瘤。生物分布和（18）F-PET成像数据清楚地表明，该方法在注射放射性配体后4小时有效地勾勒出肿瘤肿块，活性浓度高达6.4%ID/g。
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