HJAR Sep/Oct 2019

24 SEP / OCT 2019  I  HEALTHCARE JOURNAL OF ARKANSAS   Healthcare Briefs UAMS-Developed Cytophone Detects Melanoma in Earliest Stages, Could Prevent Fatal Disease Spread A University of Arkansas for Medical Sciences (UAMS) research team led by Vladimir Zharov, PhD, DSc, has demonstrated the ability to detect and kill circulating tumor cells (CTCs) in the blood using a noninvasive device called Cytophone that integrates a laser, ultrasound, and phone technologies. The device is 1,000 times more sensitive than other methods at detecting of CTCs in the blood of patients with melanoma, a deadly form of skin cancer. The Cytophone also has shown the ability to detect CTCs even when the tumor is not identifi- able on the skin, either because too small (known as the T0 or TX stage) or after surgical removal, and then to destroy them without harming sur- rounding blood cells. The team’s findings titled “In Vivo Liquid Biopsy using Cytophone Platform for Photoacoustic Detection of Circulating Tumor Cells in Mela- noma Patients” were published in the June 12 issue of Science Translational Medicine. “The only methods available to detect CTCs are mainly based on drawing blood from the patient. An average blood sample taken from a patient consists of only a few milliliters, which may or may not contain any CTCs. In contrast, the Cytophone can monitor a person’s entire five-liter blood sup- ply, potentially locating every CTC in it. No nee- dle is used, and no blood is removed,” said Zha- rov, a professor in the UAMS College of Medicine Department of Otolarynology-Head and Neck Surgery. The portable Cytophone platform is based on a principle called in vivo photoacoustic flow cytom- etry, a technology that uses laser pulses to pen- etrate through intact skin and into blood vessels to monitor circulating abnormal cells and other disease-associated biomarkers. The published research describes the first demonstration of non- invasive detection of CTCs directly in the blood- stream of melanoma patients. When a melanoma CTC passes the laser beam into the vessels, the laser pulses heat the natural melanin nanopar- ticles in these cells. The fast thermal expansion of these nanoparticles then generates a sound that is detected using an ultrasound transducer attached to the skin. The research team demonstrated that the advanced software with fast signal process- ing algorithms makes Cytophone data toler- ant to skin pigmentation and motion that led to the identification of CTCs in 96 percent of the patients in between 10 seconds and 60 minutes without generating false positives in the controls at the established thresholds and current detec- tion limit of five CTCs in five liters of blood. Researchers found that the device not only discovered CTCs in advanced stage patients, but also revealed the presence of CTCs in the patients with early Stage 2 disease. “With the Cytophone, we can listen to the laser-triggering sound from each individual cell in the body. CTCs could be one of the best early metastasis markers, because obviously only via- ble CTCs can create deadly spread of the dis- ease,” said Zharov, who also serves as director of the Arkansas Nanomedicine Center and holds the Josephine T. McGill Chair in Cancer Research at UAMS. This technology also has demonstrated the ability to destroy the detected CTCs, resulting in a large drop in CTC numbers and preventing spread of the disease to other parts of the body, known as metastasis. Thus, the Cytophone may be able to serve as a theranostic platform by integrating both diagnos- tic and therapeutic capabilities using the same laser to detect and kill the cancer cells right in the bloodstream. The Zharov team also demonstrated the Cyto- phone performance for the identification of can- cer-related blood clots, which is the second lead- ing cause of death among cancer patients. “We are developing the robust, easy-to-use portable and wearable Cytophone versions with advanced small lasers, which will be avail- able for cancer clinics across the country to start a multi-center clinical trial involving more mela- noma patients. Our goal is to determine whether Cytophone-based early diagnosis combined with destroying CTCs is effective as a stand- alone treatment or in combination with conven- tional therapies in preventing or at least inhibit- ing metastasis,” said Zharov, adding that the FDA has provided the conclusion of the Cytophone’s safety in humans. Zharov’s team first also demonstrated the abil- ity to detect non-pigmented CTCs by injecting a cocktail of magnetic and gold nanoparticles with a special biological coating into the bloodstream. Breast cancer-related clinical trials are in progress that take into account successful preclinical trials using this technology previously published in the journal Nature Nanotechnology. Other applications for the Cytophone in label- free mode could include detection of sickle cells to prevent sickle cell crisis, detection of clots to prevent stroke, and selection of the most effective drug through monitoring of circulating disease- associated markers count decrease. Zharov’s research is supported by the National Institutes of Health, including an R01 grant from the National Cancer Institute, and the National Science Foundation, among others. Collaborators on the research were Ekaterina I. Galanzha, M.D., Ph.D., D.Sc.; Yulian A. Menyaev, Ph.D.; Aayire C. Yadem, M.S.; Mustafa Sarimol- laoglu, Ph.D.; Mazen A. Juratli, M.D., Ph.D.; Dmi- try A. Nedosekin, Ph.D.; Stephen R. Foster, M.D.; Azemat Jamshidi-Parsian, M.S.; Eric R. Siegel, M.S., IssamMakhoul, M.D., Laura Hutchins, M.D.; and James Y. Suen, M.D. Additional UAMS clinic team members who supported this trial include N. Harris and A. Trammel. NYITCOM – Arkansas Hosts Project H.E.A.R.T. Summer Program More than 45 Arkansas high school students received a unique opportunity to learn about Vladimir Zharov, PhD, DSc