Acid specific dark quencher QC1 pHLIP for multi-spectral optoacoustic diagnoses of breast cancer.

TitleAcid specific dark quencher QC1 pHLIP for multi-spectral optoacoustic diagnoses of breast cancer.
Publication TypeJournal Article
Year of Publication2019
AuthorsRoberts S, Strome A, Choi C, Andreou C, Kossatz S, Brand C, Williams T, Bradbury M, Kircher MF, Reshetnyak YK, Grimm J, Lewis JS, Reiner T
JournalSci Rep
Volume9
Issue1
Pagination8550
Date Published2019 Jun 12
ISSN2045-2322
KeywordsAnimals, Cell Line, Tumor, Contrast Media, Female, Mammary Neoplasms, Experimental, Mice, Mice, Transgenic, Photoacoustic Techniques
Abstract

Breast cancer is the most common type of malignant growth in women. Early detection of breast cancer, as well as the identification of possible metastatic spread poses a significant challenge because of the structural and genetic heterogeneity that occurs during the progression of the disease. Currently, mammographies, biopsies and MRI scans are the standard of care techniques used for breast cancer diagnosis, all of which have their individual shortfalls, especially when it comes to discriminating tumors and benign growths. With this in mind, we have developed a non-invasive optoacoustic imaging strategy that targets the acidic environment of breast cancer. A pH low insertion peptide (pHLIP) was conjugated to the dark quencher QC1, yielding a non-fluorescent sonophore with high extinction coefficient in the near infrared that increases signal as a function of increasing amounts of membrane insertion. In an orthotopic murine breast cancer model, pHLIP-targeted optoacoustic imaging allowed us to differentiate between healthy and breast cancer tissues with high signal/noise ratios. In vivo, the sonophore QC1-pHLIP could detect malignancies at higher contrast than its fluorescent analog ICG-pHLIP, which was developed for fluorescence-guided surgical applications. PHLIP-type optoacoustic imaging agents in clinical settings are attractive due to their ability to target breast cancer and a wide variety of other malignant growths for diagnostic purposes. Intuitively, these agents could also be used for visualization during surgery.

DOI10.1038/s41598-019-44873-1
Alternate JournalSci Rep
PubMed ID31189972
PubMed Central IDPMC6561946
Grant ListR21 CA191679 / CA / NCI NIH HHS / United States
R01 CA212379 / CA / NCI NIH HHS / United States
R01 EB017748 / EB / NIBIB NIH HHS / United States
P30 CA008748 / CA / NCI NIH HHS / United States
R01 CA204441 / CA / NCI NIH HHS / United States
R01 CA222836 / CA / NCI NIH HHS / United States
R01 GM073857 / GM / NIGMS NIH HHS / United States