99mTc-DTPA Uptake and Electrical Impedance Measurements in Verification ofIn VivoElectropermeabilization Efficiency in Rat Muscle

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Abstract
Objective: In vivo electropermeabilization of cell membranes in rat muscle tissue cause a significant decrease of the electrical impedance, in the frequency region of 1–10 kHz. We aimed to study how the 99mTc-DTPA uptake in the electropermeabilized region correlates to the change of admittance Y = 1/absZ, where Z is the measured impedance. Methods: The electropermeabilization was performed in vivo by applying high-voltage (0.5–2 kV) short (0.1–2 ms) pulses through gold-plated needle electrodes in skeletal muscle. The impedance was measured before and after each electropermeabilization pulse. The uptake of 99mTc-DTPA uptake in the electropermeabilized region was measured after 6 and 24 hours with a gamma camera. Results: The pulse shape (square and exponential), duration, and amplitude of the applied electric field were varied, and electropermeabilization efficiency was evaluated using the various measurement modalities. Good correlations were found (correlation coefficient ≈ 0.9) between the 99mTc-DTPA uptake in the electropermeabilized and control "region of interest" the admittance ratio Y (post-treatment)/Y (pretreatment), and charge displacement parameter Q. Conclusion: The electrical impedance measurements method can be utilized in clinical settings to verify the efficiency of electropermeabilization applied to chemotherapy and to power RNAi (RNA-interference) and DNA-plasmid transfection in vaccination, immunization, and gene-therapy.