The penta-ethyl ester of diethylenetriamine pentaacetic acid (DTPA), a DTPA prodrug designated as C2E5 intended for transdermal delivery for radionuclide decorporation, was first screened with a prototype cream formulation and a hydrocarbon base ointment with C2E5 concentration ranging from 1% to 20%. C2E5 experienced rapid degradation in the cream matrix and C2E5 ointment formulation underwent phase separation due to components incompatibility. Nonaqueous gel matrix comprised of ethyl cellulose/Miglyol 840® was utilized to formulate C2E5 at different ethyl cellulose and C2E5 content levels. Differential scanning calorimetry (DSC) and scanning electron microscope (SEM) imaging were applied for analysis of the prepared C2E5 gel formulation. C2E5 was stabilized in the nonaqueous gel matrix and ethyl cellulose solubilization by dispersion media was confirmed by DSC and SEM results. Selected C2E5 nonaqueous gel formulations were evaluated in a rodent 241Am wound contamination model at a dose level of 200 mg C2E5/kg. The enhanced decorporation over no treatment control on total decorporation, decorporation by urine, and decorporation by feces was 142%, 181%, and 86%, respectively. The nonaqueous gel matrix composed of ethyl cellulose/Miglyol 840 was successfully employed to stabilize the hydrolysis prone C2E5. C2E5 was delivered transdermally and achieved enhanced decorporation for the proof of hypothesis.