Publications [#65247] of Michael R. Zalutsky

Papers Published

1. McLendon, R.E. and Archer, G.E. and Larsen, R.H. and Akabani, G. and Bigner, D.D. and Zalutsky, M.R., Radiotoxicity of systemically administered ²¹¹At-labeled human/mouse chimeric monoclonal antibody: a long-term survival study with histologic analysis, Int. J. Radiat. Oncol. Biol. Phys. (USA), vol. 45 no. 2 (1), pp. 491 - 9 [S0360-3016(99)00206-0]
   (last updated on 2007/04/15)

   Abstract:
   The antitenascin human/mouse chimeric monoclonal antibody labeled with the α-particle-emitting radionuclide ²¹¹At is of interest as an endoradiotherapeutic agent for the treatment of brain tumors. To facilitate the investigation of ²¹¹At-labeled chimeric 81C6 in patients, the long-term radiotoxicity of this radiopharmaceutical has been evaluated. Antibody labeling was performed using N-succinimidyl 3-[²¹¹At]astato-benzoate. After an initial dose-finding experiment, a second toxicity study was carried out at 4 dose levels in groups of 30 nonthyroid blocked B6C3F₁ mice per group (15 males, 15 females). Male mice received either saline or 15-81 kBq/g and females received either saline or 16-83 kBq/g of ²¹¹At-labeled antibody. Ten animals (5 males, 5 females) were followed for 6 months and the remainder for 1 year. The lethal dose in 10% of animals (LD₁₀) for ²¹¹At-labeled chimeric 81C6 was 46 kBq/g in females and 102 kBq/g in males. Toxic effects-perivascular fibrosis of the intraventricular septum of the heart, bone marrow suppression, splenic white pulp atrophy, and spermatic maturational delay-generally were confined to a few animals receiving the highest doses of labeled antibody. The LD₁₀ of ²¹¹At-labeled chimeric 81C6 in this mouse strain was about half that of [²¹¹At]astatide. These results establish the preclinical maximum tolerated dose of ²¹¹At-labeled chimeric 81C6 and define in the mouse the target organs for toxicity. These studies will be useful for determining starting doses for clinical studies with ²¹¹At-labeled chimeric 81C6

   Keywords:
   alpha-particle effects;astatine;biological effects of ionising particles;bone;brain;cardiology;health hazards;radiation therapy;radioisotopes;tumours;