Radioimmunotherapy of Cryptococcus neoformans Spares Bystander Mammalian Cells

Abstract

Background: Previously, we showed that radioimmunotherapy (RIT) for cryptococcal infections, using radioactively labeled antibodies recognizing the cryptococcal capsule, reduced fungal burden and prolonged survival of mice infected with Cryptococcus neoformans. Here, we investigate effects of RIT on bystander mammalian cells. Methods: Heat-killed C. neoformans bound to anti-capsular antibodies, unlabeled or labeled with beta emitter Rhenium-188 (16.9 h half-life), or alpha emitter Bismuth-213 (46 min half-life) was incubated with macrophage-like J774.16 cells or epithelial-like Chinese hamster ovary (CHO) cells. Lactate dehydrogenase activity, crystal violet uptake, reduction of tetrazolium dye XTT, and nitric oxide (NO) production tested cell membrane integrity, viability, replication, and effector function. Results: The J774.16 and CHO cells maintained their membrane integrity, viability and metabolic activity, and were able to replicate and to produce NO following exposure to radiolabeled C. neoformans. Conclusions: These findings show that RIT of C. neoformans is a selective and safe treatment confirming our previous observations on the absence of pathological changes in the lungs and brains of the RIT-treated mice with C. neoformans infection.JRC.E.5 - Nuclear chemistr