Diffusion-Weighted MRI for Verification of Electroporation-Based Treatments

Clinical electroporation (EP) is a rapidly advancing treatment modality that uses electric pulses to introduce drugs or genes into, e.g., cancer cells. The indication of successful EP is an instant plasma membrane permeabilization in the treated tissue. A noninvasive means of monitoring such a tissue reaction represents a great clinical benefit since, in case of target miss, retreatment can be performed immediately. We propose diffusion-weighted magnetic resonance imaging (DW-MRI) as a method to monitor EP tissue, using the concept of the apparent diffusion coefficient (ADC). We hypothesize that the plasma membrane permeabilization induced by EP changes the ADC, suggesting that DW-MRI constitutes a noninvasive and quick means of EP verification. In this study we performed in vivo EP in rat brains, followed by DW-MRI using a clinical MRI scanner. We found a pulse amplitude–dependent increase in the ADC following EP, indicating that (1) DW-MRI is sensitive to the EP-induced changes and (2) the observed changes in ADC are indeed due to the applied electric field

Calcium electroporation and electrochemotherapy for cancer treatment:Importance of cell membrane composition investigated by lipidomics, calorimetry and in vitro efficacy

Abstract Calcium electroporation is a novel anti-cancer treatment investigated in clinical trials. We explored cell sensitivity to calcium electroporation and electroporation with bleomycin, using viability assays at different time and temperature points, as well as heat calorimetry, lipidomics, and flow cytometry. Three cell lines: HT29 (colon cancer), MDA-MB231 (breast cancer), and HDF-n (normal fibroblasts) were investigated for; (a) cell survival dependent on time of addition of drug relative to electroporation (1.2 kV/cm, 8 pulses, 99 µs, 1 Hz), at different temperatures (37 °C, 27 °C, 17 °C); (b) heat capacity profiles obtained by differential scanning calorimetry without added calcium; (c) lipid composition by mass spectrometry; (d) phosphatidylserine in the plasma membrane outer leaflet using flow cytometry. Temperature as well as time of drug administration affected treatment efficacy in HT29 and HDF-n cells, but not MDA-MB231 cells. Interestingly the HT29 cell line displayed a higher phase transition temperature (approximately 20 °C) versus 14 °C (HDF-n) and 15 °C (MDA-MB231). Furthermore the HT29 cell membranes had a higher ratio of ethers to esters, and a higher expression of phosphatidylserine in the outer leaflet. In conclusion, lipid composition and heat capacity of the membrane might influence permeabilisation of cells and thereby the effect of calcium electroporation and electrochemotherapy

International Network for Sharing Practices on Electrochemotherapy (InspECT): An Integrative Patients Treatment Consortium

In this chapter we will present the International Network for Sharing Practices on Electrochemotherapy group, founded to answer the need of discussing issues and share experience on the use of the procedure, its history, and the objective for what it was established. Furthermore, on 2008 the online InspECT database was created as a tool for the Network to record data regarding clinical general examination of patients, measurement of tumor size to be treated, photographic documentation, type of anaesthesia, data on electrochemotherapy procedure, toxicity, side effects, pain, and quality of life. The amount of information stored is recorded to produce collaborative publications since all the data are entered according to the same parameters and continuously monitored according to good clinical procedures. Thanks to the collaborative work between the members of the Network it was possible to realize the publication of papers focused on specific electrochemotherapy issues. The first of them was about the management of cutaneous metastases from various solid tumors and allowed to state that electrochemotherapy offers a minimally invasive local treatment, provides local disease symptoms control, and improves patient\u2019s quality of life at the cost of only minor side effects. The second work published with the aim to evaluate which patients\u2019 category could be at risk for pain associated with electrochemotherapy identified factors related with an higher risk of postprocedural pain as diagnosis of breast cancer, treatment of preirradiated areas, largest diameter, and repetitive treatments demonstrating, however, that pain levels and pain medication overall decrease after the procedure. Finally, Bertino and Colleagues focused their attention on melanoma and nonmelanoma skin cancers of the head and neck treated with bleomycin electrochemotherapy. Electrochemotherapy resulted an effective treatment option for skin tumors of this specific area and in particular for basal cell carcinoma. The response rate in small, primary, and treatment-naive tumors is high and the functional, anatomical, and aesthetic preservation of the HN structures can be excellent at cost of well-tolerated side effects