In vivo Nachweis von metastasierenden Kopf-Hals Karzinomzellen mittels "Two-Color Photoacoustic Flow Cytometry"
Final Report Abstract
The major cause of cancer-associated mortality is tumor metastasis. CTCs, which during successful dissemination invade the surrounding primary tumor tissue, intravasate into blood, lymph and cerebrospinal fluid and could form metastasis. Therefore, one of the most promising approaches to prevent metastatic disease is the early detection of the CTCs and avoids interventions which could lead to an increase in CTC rate. The studies in this work were designed with the overall goal to determine the dynamic fluctuation of CTCs during tumor growth and medical interventions using breast cancer-, and melanoma-bearing mouse models. The PAFC and FFC allowed us to monitor the CTC dynamics noninvasively and in real-time in physiologically and clinically relevant conditions. The well-established murine xenograft mouse model was used in our studies. This model has several advantages to determine the CTC dynamic during tumor growth and medical interventions because of: (1) the use of the actual human tumor tissue; (2) results could obtained during few weeks from tumor inoculation; (3) the organ environment in which the tumor growth could reproduced However, the immunological deficit is a disadvantage for using this model. For the first time, it was possible to monitor the same mouse frequently up to eight weeks after tumor inoculation and to study the change in CTC rate during tumor compression, biopsy, and surgery. The results of this work provide further support that tumor manipulation, by offering greater opportunity for tumor cell invasion into the circulation, could result in shedding of malignant cells into the circulatory system and whether this in turn will affect the prognosis by increasing the risk of metastasis However, these data must be interpreted with caution because of the immunological deficit of our used tumor bearing-mouse models and because of the CTCs, which are rare and not all of them may be clinically relevant in the human body. Thus, further research is needed to examine CTC dynamic in human in vivo during tumor growth and medical interventions. We expect that our proposed novel diagnostic platform,in vivo PAFC with safe laser parameters can be quickly translated to humans and may catalyze a paradigm shift in diagnostic tools in clinical oncology to highly sensitive in vivo quantitative real-time monitoring of CTCs during medical interventions. If future clinical trials with in vivo PAFC dynamic monitoring of blood in cancer patients demonstrates the significance of CTC rate as an early diagnostic indicator of metastasis and a predictor of response to therapy, the proposed concept of in vivo blood test may lead to overall improved clinical outcomes and survival rates as early intervention can clearly optimize results.
Publications
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Nonlinear photoacoustic signal amplification from single targets in absorption background. Photoacoustics
Mustafa Sarimollaoglu, Dmitry A. Nedosekin, Yulian A. Menyaev, Mazen A. Juratli, and Vladimir P. Zharov
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Optical clearing in photoacoustic flow cytometry. Biomedical Optics Express, Vol. 4, Issue 12, pp. 3030-3041 (2013)
Yulian A. Menyaev, Dmitry A. Nedosekin, Mustafa Sarimollaoglu, Mazen A. Juratli, Ekaterina I. Galanzha, Valery V. Tuchin, and Vladimir P. Zharov
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Photoacoustic and photothermal detection of circulating tumor cells, bacteria and nanoparticles in cerebrospinal fluid in vivo and ex vivo. J Biophotonics. 2013 Jun;6(6-7):523-33
Nedosekin DA, Juratli MA, Sarimollaoglu M, Moore CL, Rusch NJ, Smeltzer MS, Zharov VP, Galanzha EI
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Real-time monitoring of circulating tumor cell release during tumor manipulation using in vivo photoacoustic and fluorescent flow cytometry. Head Neck. 2013 Aug 3
Mazen A. Juratli, Mustafa Sarimollaoglu, Eric R. Siegel, Dmitry A. Nedosekin, Ekaterina I. Galanzha, James Y. Suen, Vladimir P. Zharov
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Circulating cancer cell identification by functionalized silver-gold nanorods with super-enhanced SERS and photothermal resonances. Sci Rep. 2014 May 9;4:4752
Zeid Nima, Meena Mahmood, Yang Xu, Thikra Mustafa, Fumiya Watanabe, Dmitry Nedosekin, Mazen A. Juratli, Tariq Fahmi, Ekaterina Galanzha, John Nolan, Alexei Basnakian, Vladimir Zharov, and Alexandru Biris
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Dynamic Fluctuation of Circulating Tumor Cells during Cancer Progression. Cancers 2014, 6, 128-142
Mazen A. Juratli; Mustafa Sarimollaoglu; Dmetry A. Nedosekin; Yulian Melerzanov; Vladimir P. Zharov; Ekaterina I. Galanzha
