A Dose-Independent Relative Biological Effect Quantity for Targeted Alpha-Particle Therapy in the EQD2 Formalism
R Hobbs1*, G Sgouros2, R Howell3, (1) ,,,(2) Johns Hopkins Medical Institute, Baltimore, MD, (3) UMDNJ - Medical School, Newark, NJSU-E-J-184 Sunday 3:00PM - 6:00PM Room: Exhibit Hall
Purpose: Alpha particle radiopharmaceutical therapy (αRPT) is currently enjoying increasing attention as a viable alternative to chemotherapy for targeting of disseminated micrometastatic disease. The relative biological effectiveness (RBE) quantifies the different biological effects per unit absorbed dose of α particles versus traditional electron mediated radiation damage. However, the RBE is dependent on the dose and is therefore limited in its utility. We propose the adoption of a quantity, called the RBE2, a dose-independent ratio between the existing linear equivalents (i.e., EQD2s) of the different radiation doses.
Methods: Recently, the equivalent 2 Gy per fraction been chosen as the linear standard by the ICRU, denoted EQD2. Since the electron mediated dose has a linear equivalent, and the α particle dose response curve is characterized by a linear coefficient, we have chosen to define the RBE2 as the ratio between the two linear coefficients and propose to adopt it as the relevant quantity to be reported. The theoretical framework for the proposed new formalism is presented as is the application to two tumor cell lines.
Results: The radiobiological parameters are obtained by fitting the corresponding linear quadratic and linear curves to the dose response data from two cell lines: a murine breast cancer cell line, and a human breast cancer cell line. From these, the linear coefficient for both the BED and the EQD2 response lines are derived for fractionated irradiation as are the RBE values: 2.4 9.0 for the murine cell line and 2.4 - 6.0 for the human cell line. The invariant RBE2 values were 5.9 and 4.5.
Conclusion: RBE2 defined as a ratio between the electron mediated 2 Gy fraction equivalent EQD2 and the linear alpha response is independent of dosimetric endpoint and provides a more logical formalism than the dose dependent definition for data reporting and dose conversions.