99mTc-bioorthogonal click chemistry reagent for in vivo pretargeted imaging. Issue 6 (15th March 2016)

• Record Type: Journal Article
• Authors: García, María Fernanda; Zhang, Xiuli; Shah, Manankumar; Newton-Northup, Jessica; Cabral, Pablo; Cerecetto, Hugo; Quinn, Thomas
• Is Part Of: Bioorganic & medicinal chemistry. Volume 24:Issue 6(2016)
• Page Start: 1209
• Page End: 1215
• Publication Date: 2016-03-15
• Subjects: 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′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) -- RCP radiochemical purity -- EDDA ethylenediaminediacetic acid -- DMSO dimethyl sulfoxide -- SDS–PAGE sodium dodecyl sulfate polyacrylamide gel electrophoresis -- BSM bovine submaxillary glands -- CPM counts per minute -- mAb monoclonal antibody; Pretargeted imaging -- Click chemistry -- 99mTc–HYNIC -- Monoclonal antibody; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2016.01.046
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: 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 99m Tc-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 99m Tc at an efficiency of >95% and was radiochemically stable. 99m Tc–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 99m Tc–HYNIC–tetrazine for tumor imaging with pretargeted mAbs.