F-026. Cryptococcus neoformans from Mice Treated with Radioactive Antibodies to the Polysaccharide Capsule Retains Sensitivity to Radioactivity

R. A. Bryan, X. Huang, Z. Jiang, A. Casadevall, E. Dadachova;
Albert Einstein Coll. of Med., Bronx, NY.

We have previously shown protection of A/JCr mice lethally infected with Cryptococcus neoformans (CN) by treatment with radioactively labeled antibodies, using either 188-Re, a beta emitter, or 213-Bi, an alpha emitter, attached to the monoclonal antibody 18B7, which recognizes the polysaccharide capsule of CN. Our goals in this work were to fine-tune the doses to find the most effective dose, and to evaluate CN isolated from treated mice to see if it retained sensitivity to radiation. We compared doses of 100, 125, 150 and 175uCi for both isotopes, administered IP to mice 24 hours following IV infection with either 105 or 106 CN. Survival results indicated that 125uCi was the best dose for 213-Bi treatment, with 150uCi the best for 188-Re isotope. In order to evaluate the CN which survived radiation treatment, we sacrificed treated mice from the group that was treated with the optimum dose, at 3 months post infection, removed the lungs and put them through a sterile mesh, then plated on SAB agar to isolate colonies. After two days, colonies were inoculated and grown overnight in SAB broth, and then used to infect mice. Controls were CN from ATCC and from infected untreated animals. Infected animals were treated 24 hours post infection. We found that the animals infected with CN from previously treated mice showed the same weight loss and recovery as mice infected with CN controls, and the CN from radioactively treated mice had no increase in lethality compared to control CN. All groups responded similarly to radiation treatment. All had capsules of the same diameter. In vitro, all the versions of CN showed the same sensitivity to killing by 188Re or 213Bi labeled 18B7 antibody. We conclude that treatment with a single dose of radiolabeled antibody does not select for an altered population of CN.