Development and Characterization of B7-H3-specific Affibody-coated Microbubbles for Breast US Imaging

Take-Away Points

• ■ Major Focus: Improving differentiation between normal and benign breast tissue with US imaging using engineered B7-H3-specific affibody-coated microbubbles (MB_ABY-B7-H3).

• ■ Key Result: MB_ABY-B7-H3 targeting enhanced US signal from breast tumors.

• ■ Impact: Clinical development of an affibody and microbubble-based targeting agent for US may help to increase accurate breast cancer detection.

Mammography and US imaging are two widely used imaging modalities to screen and assess potential breast lesions. US imaging in particular has low sensitivity and low positive predictive value, which leads to unnecessary follow-up and biopsy collection. Thus, there is a need to develop imaging methods that better differentiate between normal and benign tissues.

Microbubbles are gas-filled lipid or protein particles that can enhance US imaging contrast due to differences in acoustic pressure upon US imaging. In recent years, microbubbles have been functionalized to target different cellular and molecular markers that would allow for a more specific signal to be observed if a breast lesion was present. B7-H3 is an emerging molecular imaging and immunotherapy target that is differentially expressed on endothelial cells surrounding benign or malignant breast tissues. Affibodies are small affinity molecules that have higher tissue penetrability than antibodies. Taken together, Bam et al developed and assessed B7-H3-specific affibody (ABY B7-H3)-coated microbubbles (MB_ABY-B7-H3) for US visualization of breast tumors in two preclinical mouse models.

In a first model, the authors use an orthotopic xenograft model with human breast MDA-MB-231 cells with MS1 endothelial cell line that did (MS_B7-H3) or did not (MS_WT) express B7-H3. A single mouse in these experiments had MDA-MB-231 tumors in both flanks that were co-engrafted with MS_B7-H3 in the left flank and MS_WT in the right flank. US imaging with MB_ABY-B7-H3 resulted in a significantly higher imaging signal in the left flank with MS_B7-H3. They additionally tested nonspecific microbubbles (MB_Non-targeted) and found that mice injected with MB_ABY-B7-H3 had higher US signal at the tumor site. The authors then performed a second experiment in a MMTV-PyMT transgenic mouse model that spontaneously develops mammary tumors expressing mouse B7-H3. Similar to the previous experiment, mice that received MB_ABY-B7-H3 had significantly higher US imaging signals than control mice that received MB_Non-targeted at the tumor site.

Taken together, the development and clinical translation of targeted microbubbles for US imaging signal enhancement may help to increase the sensitivity of breast cancer detection in the clinic.

Highlighted Article

• Bam R, Lown PS, Stern LA, et al. Efficacy of affibody-based ultrasound molecular imaging of vascular B7-H3 for breast cancer detection. Clin Cancer Res 2020;1655. doi: 10.1158/1078-0432.CCR-19-1655