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

BackgroundThe aim of this study is to elucidate the difference in absorbed dose (Dabs) patterns in radiopharmaceutical therapies between alpha emitters (225Ac) and beta emitters (177Lu) 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 (Lmean) varied throughout these models from 92 to 1030 µm. Dabs calculations were performed while selecting either CAFs or tumor cells as sources, with Convolution/Superposition with 177Lu and Monte Carlo simulations (GATE) with 225Ac. Analyses were conducted with Dose Volume Histograms and efficacy ratios (ER), which represents the ratio of mean Dabs that is deposited in the target volume.Results225Ac is the most optimal radionuclide when CAFs are both targeted and irradiating themselves, as ERs increase from 1.5 to 3.7 when Lmean increases from 92 to 1030 µm. With 177Lu, these numbers vary from 1.2 to 2.7. Conversely, when CAFs are sources and tumors are targets with 225Ac, ERs decreased from 0.8 to 0.1 when Lmean increases from 92 to 1030 µm. With 177Lu, these numbers vary from 0.9 to 0.3 CONCLUSION: When targeting CAFs to irradiate tumors, the efficacy of using 225Ac decreases as the average size of the tumor clusters (or Lmean) increases. In such situations, 177Lu will be more effective than 225Ac when targeting CAFs due to the longer beta particle range