Microbial Cytotoxic Effect of 212Pb in Radiopharmaceuticals.

Background: The cytotoxic effect of ²¹²Pb on microbial growth was examined, using six microorganisms, at clinically relevant time points, to determine the potency of ²¹²Pb as a self-sterilizing agent in radiopharmaceuticals using [²¹²Pb]Pb-DOTAMTATE. Materials and Methods: Vials of radiolabeled [²¹²Pb]Pb-DOTAMTATE, nonradiolabeled DOTAMTATE, and appropriate media were inoculated with Bacillus spizizenii, Candida albicans, Clostridium sporogenes, Pseudomonas aeruginosa, Staphylococcus aureus, or Aspergillus brasiliensis. Samples from each vial type were plated onto tryptic soy agar or Sabouraud dextrose plates and allowed to grow at optimal temperature for each strain to obtain quantifiable colony forming units (CFU). Results: Each microbial organism observed at least a 6 log reduction in total CFUs after 6 h of exposure to [²¹²Pb]Pb-DOTAMTATE drug product vials, showing no remaining colonies as compared to the vials containing only media and drug formulation with no radiolabeled material, utilizing a low absorbed dose of no greater than 1.01 kGy. A sterility assessment of the two [²¹²Pb]Pb-DOTAMTATE drug product vials containing the lowest total CFUs per vial displayed no microbial growth upon incubation for 14 d. Conclusions: This study suggests that ²¹²Pb in radiopharmaceuticals is a potent microbial cytotoxic agent with self-sterilizing properties.