Relative biological effectiveness (RBE)

Relative biological effectiveness (RBE) is defined as the ratio of the absorbed dose of a reference radiation (conventionally x-rays, gamma rays, or a beta emitter) to the absorbed dose of a test radiation required to produce an identical biological effect under otherwise identical conditions: RBE = D(reference)/D(test) for the same endpoint. Unlike the fixed, consensus-based radiation weighting factor (wR) used in the regulatory quantity equivalent dose, RBE is an empirically measured quantity that varies with the specific biological endpoint studied (cell survival, organ toxicity, tumour control), the dose and dose rate, the cell type, and oxygen tension, so a single RBE value cannot be assumed to apply across all contexts.

For targeted alpha therapy, RBE values for cell-kill endpoints are commonly reported in the range of roughly 3 to 8 relative to external-beam or beta reference radiation, though for stochastic cancer-induction endpoints regulatory bodies use a flat wR of 20 for alpha particles, illustrating why RBE and wR are not interchangeable. In actinium-225 versus lutetium-177 dosimetry specifically, experimental work using DNA double-strand-break markers has reported RBE values around 5, and this figure has been used as a practical multiplier to convert measured absorbed dose in gray into an RBE-weighted dose estimate when comparing alpha and beta radioligand therapies or predicting organ toxicity.

RBE is central to interpreting and comparing dosimetry across the beta-to-alpha pairing strategy in radioligand therapy (for example, sequencing lutetium-177 PSMA therapy with actinium-225 PSMA therapy), because a modest gray value from an alpha emitter can correspond to a much larger biologically effective dose than the same gray value from a beta emitter.