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. 2021 May 5;19:128. doi: 10.1186/s12951-021-00871-y

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© The Author(s) 2021

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 6 — Iso1Au/TNF reduces tumor perfusion. WEHI 164 tumor-bearing mice (n = 6/group) were treated i.v. with the indicated dose of iso1Au/TNF at day 6 after tumor implantation and were analyzed by contrast-enhanced ultrasound (CEUS) at day 8 (3 mice) and day 9 (3 mice). MicroMarker Contrast Agent was injected at time 0, and its uptake was recorded for 40 s. a Scheme of the experiment. b Effect of iso1Au/TNF (5 pg) or vehicle on tumor growth before and after treatment (day 1), as determined by calipers. c Time-intensity curves (mean ± SE); ****p < 0.0001, by two-way ANOVA. d Grayscale tumor images (left) and color-coded peak enhancement (PE) maps of representative mice. Red and blue areas correspond to high and low perfused tumor areas, respectively. Numbers, PE values. e Quantitative analysis of tumor perfusion with microbubbles performed using VevoCQTM software. CEUS parameters were calculated using a region of interest (ROI, green lines in d) corresponding to the entire tumor area. Box plots of CEUS parameters with 5–95 percentiles and medians are shown; *P < 0.05; **P < 0.001 by two-tailed t-test. Images were taken at regions with a maximum tumor diameter. f Tumor weight at day 10