Rodriguez Erik A, Wang Ye, Crisp Jessica L, Vera David R, Tsien Roger Y, Ting Richard
Department of Pharmacology, University of California, San Diego, La Jolla, California 92093, United States.
Molecular Imaging Innovations Institute (MI3), Department of Radiology, Weill Cornell Medicine, New York, New York 10065, United States.
Bioconjug Chem. 2016 May 18;27(5):1390-1399. doi: 10.1021/acs.bioconjchem.6b00164. Epub 2016 Apr 27.
New protecting group chemistry is used to greatly simplify imaging probe production. Temperature and organic solvent-sensitive biomolecules are covalently attached to a biotin-bearing dioxaborolane, which facilitates antibody immobilization on a streptavidin-agarose solid-phase support. Treatment with aqueous fluoride triggers fluoride-labeled antibody release from the solid phase, separated from unlabeled antibody, and creates [(18)F]-trifluoroborate-antibody for positron emission tomography and near-infrared fluorescent (PET/NIRF) multimodality imaging. This dioxaborolane-fluoride reaction is bioorthogonal, does not inhibit antigen binding, and increases [(18)F]-specific activity relative to solution-based radiosyntheses. Two applications are investigated: an anti-epithelial cell adhesion molecule (EpCAM) monoclonal antibody (mAb) that labels prostate tumors and Cetuximab, an anti-epidermal growth factor receptor (EGFR) mAb (FDA approved) that labels lung adenocarcinoma tumors. Colocalized, tumor-specific NIRF and PET imaging confirm utility of the new technology. The described chemistry should allow labeling of many commercial systems, diabodies, nanoparticles, and small molecules for dual modality imaging of many diseases.
新的保护基团化学方法被用于极大地简化成像探针的生产。对温度和有机溶剂敏感的生物分子被共价连接到带有生物素的二氧杂硼烷上，这有助于抗体固定在链霉亲和素 - 琼脂糖固相支持物上。用氟化水溶液处理会促使氟标记的抗体从固相中释放出来，与未标记的抗体分离，并生成用于正电子发射断层扫描和近红外荧光（PET/NIRF）多模态成像的[(18)F] - 三氟硼酸酯 - 抗体。这种二氧杂硼烷 - 氟化物反应是生物正交的，不抑制抗原结合，并且相对于基于溶液的放射性合成提高了[(18)F]的比活度。研究了两种应用：一种标记前列腺肿瘤的抗上皮细胞粘附分子（EpCAM）单克隆抗体（mAb）和西妥昔单抗，一种标记肺腺癌肿瘤的抗表皮生长因子受体（EGFR）mAb（已获美国食品药品监督管理局批准）。共定位的肿瘤特异性NIRF和PET成像证实了这项新技术的实用性。所描述的化学方法应该能够对许多商业系统、双特异性抗体、纳米颗粒和小分子进行标记，用于多种疾病的双模态成像。
