Multimodal Imaging Techniques to Evaluate the Anticancer Effect of Cold Atmospheric Pressure Plasma

SIMPLE SUMMARY: Skin cancer still poses a great burden for patients. One of the most promising therapy approaches in recent years is cold atmospheric pressure plasma. The aim of the study was to assess in vivo the effect of cold atmospheric pressure plasma on human squamous cell carcinoma as well as malignant melanoma tumour cell lines in a longitudinal and non-invasive manner with multimodal imaging techniques such as MRI and [18F]FDG PET. By using these techniques and chemiluminescence imaging, we present in the current study that reactive species increase in vivo upon treatment with cold plasma and consequently decrease tumour growth. Therefore, we propose cold atmospheric pressure plasma may be a potential adjuvant therapy option to established standard therapies of skin cancer. ABSTRACT: Background: Skin cancer is the most frequent cancer worldwide and is divided into non-melanoma skin cancer, including basal cell carcinoma, as well as squamous cell carcinoma (SCC) and malignant melanoma (MM). Methods: This study evaluates the effects of cold atmospheric pressure plasma (CAP) on SCC and MM in vivo, employing a comprehensive approach using multimodal imaging techniques. Longitudinal MR and PET/CT imaging were performed to determine the anatomic and metabolic tumour volume over three-weeks in vivo. Additionally, the formation of reactive species after CAP treatment was assessed by non-invasive chemiluminescence imaging of L-012. Histological analysis and immunohistochemical staining for Ki-67, ApopTag(®), F4/80, CAE, and CD31, as well as protein expression of PCNA, caspase-3 and cleaved-caspase-3, were performed to study proliferation, apoptosis, inflammation, and angiogenesis in CAP-treated tumours. Results: As the main result, multimodal in vivo imaging revealed a substantial reduction in tumour growth and an increase in reactive species after CAP treatment, in comparison to untreated tumours. In contrast, neither the markers for apoptosis, nor the metabolic activity of both tumour entities was affected by CAP. Conclusions: These findings propose CAP as a potential adjuvant therapy option to established standard therapies of skin cancer.