Intraoperative tumor margin assessment during breast-conserving surgical resection is critically needed as positive margins are found in up to 34% of patients. Spectroscopic photoacoustic (sPA) molecular imaging combined with translatable antibody (Ab)-indocyanine green (ICG) contrast agent targeted to B7-H3, a molecular marker differentially expressed in breast cancer, may aid in margin assessment in murine breast cancers. ICG was conjugated to anti-B7-H3 antibodies through standard NHS chemistry. FVB/N Tg(MMTV/PyMT634Mul mice, a transgenic mouse model for breast cancer development, 5 weeks of age with ductal carcinoma in situ (DCIS) or small invasive carcinomas were given 33 μg of B7-H3-ICG 3-5 days before surgical resection. During excision of sequential sections of the lower mammary glands, fluorescence, multi-wavelength (680-900 nm, 10 nm increments) sPA, and B-mode ultrasound imaging were performed. Section specific molecular B7-H3 signal was compared to fluorescence imaging and histological (H&E) analysis. B-mode US and sPA imaging signal were able to relay accurate anatomical and molecular tissue information. sPA molecular imaging was able to detect B7-H3-ICG uptake in DCIS and early invasive carcinomas less than 1 mm in diameter. Furthermore, histological analysis of the excised tissues was able to show strong correlation between sPA imaging signal and disease state and location. While fluorescence imaging was able to detect ICG signal, there was insufficient resolution and specificity to identify and aid in resection of small cancerous foci. Adding molecular sPA imaging to help guide intraoperative margin assessment may increase the occurrence of negative margins which will decrease local disease recurrence.
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