Publications [#65217] of Michael R. Zalutsky

Papers Published

1. Akabani, G. and McLendon, R.E. and Bigner, D.D. and Zalutsky, M.R., Vascular targeted endoradiotherapy of tumors using alpha-particle-emitting compounds: theoretical analysis, Int. J. Radiat. Oncol. Biol. Phys. (USA), vol. 54 no. 4 (2002), pp. 1259 - 75 [S0360-3016(02)03794-X]
   (last updated on 2007/04/15)

   Abstract:
   Our purpose was to establish the theoretical framework and study the feasibility of ²¹¹At-labeled anti-tenascin chimeric 81C6 monoclonal antibody (mAb) as anti-vascular endoradiotherapy for the treatment of glioblastoma multiforme (GBM) tumors. The morphology of blood vessels from histologic images was analyzed and used along with reaction-diffusion equations to assess the activity concentration of ²¹¹At-labeled chimeric 81C6 mAb in GBM tumor and normal-brain tissue. Alpha particle microdosimetry was then used to assess the survival probability and average absorbed dose for tumor and normal tissue endothelial cells (ECs) per unit vascular cumulated activity concentration q_source (MBq-s g^-1). In turn, these survival probabilities were used to assess the probability of failure Φ for a single vessel. Furthermore, using the vessel density, the specific tumor control probability per unit mass of tumor tissue (tcp) and the specific normal-tissue complication probability per unit mass of normal-brain tissue (ntcp) were estimated. The specific tumor control probability, tcp, was used to assess the overall tumor control probability (TCP) as a function of tumor mass. The levels of ²¹¹At-labeled ch81C6 mAb cumulated activity concentration in GBM tumor tissue were approximately five times higher than that in normal-brain tissue. Thus, the average absorbed dose to tumor ECs was higher than that of normal tissue ECs, and the survival probability for GBM ECs was lower than for normal-brain tissue ECs. Consequently, the resulting vessel-failure probability, Φ, for GBM tumor and for normal-brain tissue differ considerably, yielding a q_source range between 10³ and 10⁴ MBq-s g^-1. In conclusion, this theoretical analysis demonstrated that ²¹¹At-labeled chimeric 81C6 is an effective antivascular therapy for the treatment of GBM tumors, yielding a tcp higher than 0.999 for vascular cumulated activity concentrations q_source higher than 1 × 10⁴ MBq-s g^-1, while yielding a low probability for normal-brain tissue damage

   Keywords:
   alpha-particle sources;blood vessels;brain;probability;radiation therapy;tumours;