Impact of radiopharmaceutical therapy ((177)Lu, (225)Ac) microdistribution in a cancer-associated fibroblasts model

BACKGROUND: The aim of this study is to elucidate the difference in absorbed dose (D(abs)) patterns in radiopharmaceutical therapies between alpha emitters ((225)Ac) and beta emitters ((177)Lu) when targeting cancer-associated fibroblasts (CAF) or tumor cells. Five spherical models with 3 mm diameter were created, representing spherical tumor masses that contain tumor clusters, interspersed with CAFs. The mean distance from a tumor cell to the nearest CAF (L(mean)) varied throughout these models from 92 to 1030 µm. D(abs) calculations were performed while selecting either CAFs or tumor cells as sources, with Convolution/Superposition with (177)Lu and Monte Carlo simulations (GATE) with (225)Ac. Analyses were conducted with Dose Volume Histograms and efficacy ratios (ER), which represents the ratio of mean D(abs) that is deposited in the target volume. RESULTS: (225)Ac is the most optimal radionuclide when CAFs are both targeted and irradiating themselves, as ERs increase from 1.5 to 3.7 when L(mean) increases from 92 to 1030 µm. With (177)Lu, these numbers vary from 1.2 to 2.7. Conversely, when CAFs are sources and tumors are targets with (225)Ac, ERs decreased from 0.8 to 0.1 when L(mean) increases from 92 to 1030 µm. With (177)Lu, these numbers vary from 0.9 to 0.3 CONCLUSION: When targeting CAFs to irradiate tumors, the efficacy of using (225)Ac decreases as the average size of the tumor clusters (or L(mean)) increases. In such situations, (177)Lu will be more effective than (225)Ac when targeting CAFs due to the longer beta particle range. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40658-022-00497-5.