A microdosimetric model of astatine-211 labeled antibodies for radioimmunotherapy.
Astatine-211 is an alpha-emitter with a short half-life (7.2 hr). This paper discusses the potential of 211At targeted by antibodies for tumor therapy and the possible advantage of 211At over beta- and gamma-emitting radionuclides such as 131I currently employed in the field of radioimmunotherapy. Since the longest range alpha-particle from 211At is only 67 microns and the rate of energy loss is high (track averaged linear energy transfer LT approximately 120 keV/micron), a disintegration of 211At produces a large and extremely localized deposition of energy. A Monte-Carlo model has been developed for studying the stochastic fluctuation of alpha-particle hits and energy deposition in cell nuclei in an attempt to determine the efficacy of 211At-labeled antibodies for tumor cell inactivation. Calculations have been performed for 2 extreme conditions: (a) the case of 211At retained in the capillary, and (b) for a homogeneous distribution of 211At-labeled antibody in the tumor. The results of these two calculations represent the boundary conditions between which any real solution must lie. Finally, developments to the model to include antibody transport across the capillary membrane and through the tumor tissue are discussed.
Humm
J L
JL
MRC Radiobiology Unit, Chilton, Didcot, Oxon, U.K.
D000912:Antibodies, Neoplasm / Q000008:administration & dosage*; D001246:Astatine / Q000008:administration & dosage*; D006801:Humans; D007167:Immunotherapy; D009010:Monte Carlo Method; D009369:Neoplasms / Q000532:radiotherapy* / Q000628:therapy*; D009874:Operations Research; D011880:Radiotherapy Planning, Computer-Assisted; D011881:Radiotherapy, Computer-Assisted
D000912:Antibodies, Neoplasm; D001246:Astatine