Photoacoustic imaging reveals transient decrease of oxygenation in murine blood due to monoclonal IgG4 antibody

Creators: Khadria, Anjul; Paavola, Chad D.; Maslov, Konstantin; Brown-Augsburger, Patricia L.; Grealish, Patrick F.; Lozano, Emmanuel; Blankenship, Ross L.; Cao, Rui; Shi, Junhui; Beals, John M.; Oladipupo, Sunday S.; Wang, Lihong V.

Abstract

Over 100 monoclonal antibodies have been approved by the FDA for clinical use; however, a paucity of knowledge exists regarding the injection site behavior of these formulated therapeutics, i.e., the effect of antibody and formulation on the tissue around the injection site and vice versa. In this report, we injected a near-infrared dye-labeled IgG4 isotope control antibody into the subcutaneous space in mouse ears to analyze the injection site dynamics, including quantifying molecular movement. Surprisingly, we discovered that the antibody reduces the local blood oxygen saturation levels in mice after prolonged anesthesia without affecting the total hemoglobin content and oxygen extraction fraction. The local oxygen saturation results open a new pathway to study the functional effects of monoclonal antibodies.

Additional Information

The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license. Data availability. The data that support the conclusions are mentioned in the main draft or the supplementary information. Author contributions. L.V.W., S.O., J.M.B., C.D.P., and A.K. conceived the project and the ideas. C.D.P. and A.K. designed the chemistry and parameters for dye labeling. P.G. labeled the antibody with the dye and characterized them. P.G. and A.K. prepared the antibody and dye buffer solutions. A.K. and K.M. designed and built the scanning photoacoustic microscope. A.K. designed and performed all the photoacoustic experiments and analyzed all the photoacoustic data. R.C. and J.S. wrote the LabVIEW software for photoacoustic data acquisition. P.B.A., E.L., and R.L.B. designed, performed, and analyzed the pharmacokinetic experiments. L.V.W., S.O., and J.M.B. supervised the project. A.K. wrote the manuscript. C.D.P., P.B.A., J.M.B, S.O., and LV.W. contributed to writing the manuscript. Competing Interest Statement. A.K., R.C., and J.S. declare no competing interests. C.D.P., P.G, P.L.B.A., E.L., R.L.B, J.M.B, and S.O. are employees and stockholders of Eli Lilly and Company. L.V.W. and K.M. have financial interests in Microphotoacoustics, Inc., CalPACT, LLC, and Union Photoacoustic Technologies, Ltd, which did not support this work.

Attached Files

Submitted - 2022.09.29.509334v1.full.pdf

Supplemental Material - media-1.pdf

Files

2022.09.29.509334v1.full.pdf

Files (3.2 MB)

Name	Size	Download all
2022.09.29.509334v1.full.pdf md5:8858be14254cf885fdd5cb40a860ed44	2.6 MB	Preview Download
media-1.pdf md5:69a3812d70cfbf209aa64f8c7b714233	658.6 kB	Preview Download

Additional details

	All versions	This version
Views	0	0
Downloads	0	0
Data volume	0 Bytes	0 Bytes