Cell-level dosimetry and biologic response modeling of heterogeneously distributed radionuclides: a step forward.

Historically, clinical response to internal radionuclides has been related to the macroscopic (i.e., whole-tumor or whole-organ) absorbed dose, implicitly assuming uniform distributions of activity and energy deposition (1,2). However, the actual biologic response among cells within a tumor or organ can vary substantially, depending on spatial nonuniformities of these distributions at the multicellular, cellular, and subcellular levels (3–9). The macroscopic, or mean, absorbed dose thus may not be a reliable descriptor of the biologic effect of internally deposited