TY - JOUR
T1 - Simultaneous Photoradiochemical Labeling of Antibodies for Immuno-Positron Emission Tomography
AU - Patra, Malay
AU - Klingler, Simon
AU - Eichenberger, Larissa S.
AU - Holland, Jason P.
N1 - Publisher Copyright:
© 2019 The Author(s)
PY - 2019/3/29
Y1 - 2019/3/29
N2 - 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.
AB - 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.
KW - Density Functional Theory (DFT)
KW - Medical Imaging
KW - Radiochemicals
UR - http://www.scopus.com/inward/record.url?scp=85066335991&partnerID=8YFLogxK
U2 - 10.1016/j.isci.2019.03.004
DO - 10.1016/j.isci.2019.03.004
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AN - SCOPUS:85066335991
SN - 2589-0042
VL - 13
SP - 416
EP - 431
JO - iScience
JF - iScience
ER -