title: Noninvasive in vivo multispectral optoacoustic imaging of apoptosis in triple negative breast cancer using indocyanine green conjugated phosphatidylserine monoclonal antibody.
abstract: Noninvasive and nonradioactive imaging modality to track and image apoptosis during chemotherapy of triple negative breast cancer is much needed for an effective treatment plan. Phosphatidylserine (PS) is a biomarker transiently exposed on the outer surface of the cells during apoptosis. Its externalization occurs within a few hours of an apoptotic stimulus by a chemotherapy drug and leads to presentation of millions of phospholipid molecules per apoptotic cell on the cell surface. This makes PS an abundant and accessible target for apoptosis imaging. In the current work, we show that PS monoclonal antibody tagged with indocyanine green (ICG) can help to track and image apoptosis using multispectral optoacoustic tomography <italic<in vivo</italic<. When compared to saline control, the doxorubicin treated group showed a significant increase in uptake of ICG-PS monoclonal antibody in triple negative breast tumor xenografted in NCr nude female mice. Day 5 posttreatment had the highest optoacoustic signal in the tumor region, indicating maximum apoptosis and the tumor subsequently shrank. Since multispectral optoacoustic imaging does not involve the use of radioactivity, the longer the circulatory time of the PS antibody can be exploited to monitor apoptosis over a period of time without multiple injections of commonly used imaging probes such as Tc-99m Annexin V or F-18 ML10. The proposed apoptosis imaging technique involving multispectral optoacoustic tomography, monoclonal antibody, and near-infrared absorbing fluorescent marker can be an effective tool for imaging apoptosis and treatment planning.
authors.affiliation: Singapore General Hospital, Department of Nuclear Med and PET, Outram Road, Singapore 169608, Singapore.
authors.forename: Ravi Kumar
authors.initials: RK
authors.lastname: Kannadorai
authors.affiliation: Singapore General Hospital, Radiological Sciences Academic Clinical Program, Outram Road, Singapore 169608, Singapore.
authors.forename: Sunil Kumar
authors.initials: SK
authors.lastname: Udumala
authors.affiliation: Singapore General Hospital, Department of Nuclear Med and PET, Outram Road, Singapore 169608, Singapore.
authors.forename: Yu Wing Kwong
authors.initials: YW
authors.lastname: Sidney
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D005260:Female; D007208:Indocyanine Green / Q000493:pharmacokinetics* / Q000494:pharmacology; D051379:Mice; D008819:Mice, Nude; D061848:Optical Imaging / Q000379:methods*; D010718:Phosphatidylserines / Q000493:pharmacokinetics* / Q000494:pharmacology; D061088:Photoacoustic Techniques / Q000379:methods*; D064726:Triple Negative Breast Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D010718:Phosphatidylserines; D007208:Indocyanine Green