title: In vivo photoacoustic imaging of chemotherapy-induced apoptosis in squamous cell carcinoma using a near-infrared caspase-9 probe.
abstract: Anti-cancer drugs typically exert their pharmacological effect on tumors by inducing apoptosis, or programmed cell death, within the cancer cells. However, no tools exist in the clinic for detecting apoptosis in real time. Microscopic examination of surgical biopsies and secondary responses, such as morphological changes, are used to verify efficacy of a treatment. Here, we developed a novel near-infrared dye-based imaging probe to directly detect apoptosis with high specificity in cancer cells by utilizing a noninvasive photoacoustic imaging (PAI) technique. Nude mice bearing head and neck tumors received cisplatin chemotherapy (10 mg/kg) and were imaged by PAI after tail vein injection of the contrast agent. In vivo PAI indicated a strong apoptotic response to chemotherapy on the peripheral margins of tumors, whereas untreated controls showed no contrast enhancement by PAI. The apoptotic status of the mouse tumor tissue was verified by immunohistochemical techniques staining for cleaved caspase-3 p11 subunit. The results demonstrated the potential of this imaging probe to guide the evaluation of chemotherapy treatment.
authors: University of Kansas, Department of Pharmaceutical Chemistry, Lawrence, Kansas 66047, USA.
authors: Qiuhong
authors: Q
authors: Yang
authors: Huizhong
authors: H
authors: Cui
authors: Shuang
authors: S
authors: Cai
authors: Xinmai
authors: X
authors: Yang
authors: M Laird
authors: ML
authors: Forrest
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism*; D002945:Cisplatin / Q000494:pharmacology; D005260:Female; D005456:Fluorescent Dyes / Q000737:chemistry; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D007150:Immunohistochemistry; D051379:Mice; D008819:Mice, Nude; D057054:Molecular Imaging / Q000379:methods; D015335:Molecular Probes / Q000737:chemistry*; D061088:Photoacoustic Techniques / Q000379:methods*; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D000970:Antineoplastic Agents; D005456:Fluorescent Dyes; D015335:Molecular Probes; D053148:Caspase 3; D053453:Caspase 9; D002945:Cisplatin