Tc-99m pyrophosphate imaging of poloxamer-treated electroporated skeletal muscle in an in vivo rat model

Abstract

Objective This study investigates whether 99mTc pyrophosphate (PYP) imaging provides a quantitative non-invasive assessment of the extent of electroporation injury, and of the effect of poloxamer in vivo on electroporated skeletal muscle. Methods High-voltage electrical shock was used to produce electroporation injury in an anesthetized rat's hind limb. In each experiment, the injured limb was treated intravenously by either poloxamer-188, dextran, or saline, and subsequently imaged with 99mTc PYP. The radiotracer's temporal behavior among the experimental groups was compared using curve fitting of time–activity curves from the dynamic image data. Results The washout kinetics of 99mTc PYP changed in proportion to the electric current magnitude that produced electroporation. Also, 99mTc PYP washout from electroporated muscle differed between poloxamer-188 treatment and saline treatment. Finally, 10-kDa dextran treatment of electroporated muscle altered 99mTc PYP washout less than poloxamer-188 treatment. Conclusions Behavior of 99mTc PYP in electroporated muscle appears to be an indicator of the amount of electroporation injury. Compared to saline, intravenous polaxamer-188 treatment reduced the amount of 99mTc PYP uptake. Coupled to results showing poloxamer-188 seals ruptured cellular membranes, lessens the extent of electroporation injury and improves cell viability, 99mTc PYP imaging appears to be a useful in vivo monitoring tool for the extent of electroporation injury.