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. 2022 Sep 12;10(9):e005199. doi: 10.1136/jitc-2022-005199

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© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See http://creativecommons.org/licenses/by-nc/4.0/.

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Sensitive monitoring of anti-CD47 therapy response by dynamic metabolic imaging of NAD(P)H. (A, B) Label-free metabolic intravital imaging (LMII) of NAD(P)H demonstrates sensitive early response at single-cell level after anti-CD47 mAb (MIAP301) treatment of a triple-negative breast cancer model (10 mg/kg intravenous injection daily for 5 days). (C) Quantification of average intensity shows statistically significant difference in NAD(P)H signals before and after MIAP301 treatment (n=16 images, p<0.0001). (D) Kinetics of single-cell metabolism with NAD(P)H signal. Each colored small square represents the visible pixel intensity of NAD(P)H in each cancer cell. The 10,000-pixel intensities were randomly measured from the cells in different mice every day for 16 days (n=6 mice). Metabolic signal of NAD(P)H has been increased with tumor growth from day 1 to day 9 and dramatically decreased with start of anti-CD47 mAb treatment from day 10. (E, F) Conventional whole-body bioluminescence imaging of 4T1_PB3R-RFP-luc tumor mice verified cancer treatment with increased signal before anti-CD47 therapy and decreased signal after the therapy compared with isotype control treatment (n=6 mice). LMII shows superior sensitivity to detect immunotherapy response (p<0.0001 in C) over bioluminescence imaging (p=0.0122 in F). (G) Flow cytometric analysis shows decrease of NAD(P)H and RFP signals with CD47 inhibitor treatment over isotype control treatment. (H) The signal from NAD(P)H+RFP+ cells was significantly decreased after MIAP301 treatment when compared with isotype control as determined by flow cytometry (n=11 mice, p=0.0043). CD47, cluster of differentiation 47; mAb, monoclonal antibody; NAD(P)H, reduced nicotinamide adenine dinucleotide (phosphate) hydrogen; RFP, red fluorescent protein.