Vascular targeted endoradiotherapy of tumors using alpha-particle-emitting compounds: theoretical analysis.
OBJECTIVE
To establish the theoretical framework and study the feasibility of (211)At-labeled anti-tenascin chimeric 81C6 monoclonal antibody (mAb) as anti-vascular endoradiotherapy for the treatment of glioblastoma multiforme (GBM) tumors.


METHODS
The morphology of blood vessels from histologic images was analyzed and used along with reaction-diffusion equations to assess the activity concentration of (211)At-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 Phi 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.


RESULTS
The levels of (211)At-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, Phi, for GBM tumor and for normal-brain tissue differ considerably, yielding a q(source) range between 10(3) and 10(4) MBq-s g(-1).


CONCLUSIONS
This theoretical analysis demonstrated that (211)At-labeled chimeric 81C6 is an effective anti-vascular therapy for the treatment of GBM tumors, yielding a tcp higher than 0.999 for vascular cumulated activity concentrations q(source) higher than 1 x 10(4) MBq-s g(-1), while yielding a low probability for normal-brain tissue damage.
Akabani
Gamal
G
Department of Radiology, Duke University Medical Center, Box 3808, Durham, NC 27710, USA. akaba001@mc.duke.edu
McLendon
Roger E
RE
Bigner
Darrell D
DD
Zalutsky
Michael R
MR
D000512:Alpha Particles / Q000627:therapeutic use*; D001246:Astatine / Q000627:therapeutic use*; D016754:Boron Neutron Capture Therapy; D001921:Brain / Q000528:radiation effects; D001932:Brain Neoplasms / Q000532:radiotherapy*; D005909:Glioblastoma / Q000532:radiotherapy*; D006801:Humans; D011336:Probability; D016499:Radioimmunotherapy; D011874:Radiometry; D019063:Tenascin / Q000276:immunology*
D019063:Tenascin; D001246:Astatine