Development and Evaluation of ^99mTc-Amphotericin Complexes as Potential Diagnostic Agents in Nuclear Medicine

Abstract

Background: Invasive fungal infections have become highly relevant due to the exponential increase in the population, whose immune non mycotic foci by gamma scintigraphy would allow the appropriate treatment of the patient and avoid the appearance of irreversible tissue damage. Objectives: The present study aimed at development and evaluation of amphotericin B and 99mTc complexes as potential radiopharmaceuticals for the diagnosis of fungal infections by gamma scintigraphy. Methods: Amphotericin was radiolabeled with 99mTc-tricarbonyl and 99mTc-nitride precursors. The complexes were assessed for in vitro stability, lipophilicity, plasma protein binding, plasma stability, and yeast union. Biological evaluation was conducted in 4 groups of CD1 female mice. G0 healthy animals and G1 were induced sterile inflammation with turpentine oil. G2 and G3 were infected with Candida albicans and Aspergillus niger. Results: 99mTc-amphotericin complexes were obtained with radiochemical purity (RCP) higher than 90%, and both were stable in labelling milieu for at least 20 hours and in plasma for 4 hours. Biodistributions of 99mTc(CO)3-amphotericin revealed that the complex was well tolerated by mice and showed mainly urinary excretion. Lesion uptake was 3 times higher in infected tissues with Candida albicans than in sterile inflammation. Conclusions: The 99mTc(CO)3-amphotericin complex is outlined as a potential diagnostic agent for fungal infections by gamma scintigraphy.