Simultaneous Photoradiochemical Labeling of Antibodies for Immuno-Positron Emission Tomography

• Published in: iScience Vol. 13; pp. 416 - 431
• Main Authors: Patra, Malay, Klingler, Simon, Eichenberger, Larissa S., Holland, Jason P.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 29.03.2019; Elsevier
• Subjects: Density Functional Theory (DFT); Medical Imaging; Radiochemicals; Radiochemicals; Density Functional Theory (DFT); Medical Imaging
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2019.03.004

A method for the simultaneous (one-step) photochemical conjugation and 89Zr-radiolabeling of antibodies is introduced. A photoactivatable chelate based on the functionalization of desferrioxamine B with an arylazide moiety (DFO-ArN3, [1]) was synthesized. The radiolabeled complex, 89Zr-1+, was produced and characterized. Density functional theory calculations were used to investigate the mechanism of arylazide photoactivation. 89Zr-radiolabeling experiments were also used to determine the efficiency of photochemical conjugation. A standard two-step approach gave a measured conjugation efficiency of 3.5% ± 0.4%. In contrast, the one-step process gave a higher photoradiolabeling efficiency of ∼76%. Stability measurements, cellular saturation binding assays, positron emission tomographic imaging, and biodistribution studies in mice bearing SK-OV-3 tumors confirmed the biochemical viability and tumor specificity of photoradiolabeled [89Zr]ZrDFO-azepin-trastuzumab. Experimental data support the conclusion that the combination of photochemistry and radiochemistry is a viable strategy for producing radiolabeled proteins for imaging and therapy. [Display omitted] •Photochemistry is combined with radiochemistry for radiosynthesis in a flash•Simultaneous photoradiochemistry is achieved with high radiolabeling efficiency•Photoradiochemistry produces viable 89Zr-radiolabeled antibodies•Density functional theory calculations elucidate the photoactivation mechanism Density Functional Theory (DFT); Medical Imaging; Radiochemicals