Preclinical Lutetium-177 Intracellular Dosimetry of Target Cancers in Radionuclide Therapy

Purpose: This study investigates the preclinical dosimetry of Lutetium-177 in targeted radionuclide therapy for cancer treatment, focusing on the radiopharmaceutical [ 177 Lu] Lu-DOTATATE. Materials and Methods: Subcutaneous HT-29 xenografts were established in nu/nu mice and administered [ 177 Lu] Lu-DOTATATE intravenously. Tumor uptake was quantified by radiometry, and absorbed doses were calculated using MIRD formalism and a linear-quadratic model to determine cell death probability. Results: Using HT-29 tumor cell xenografts in nude mice, the research evaluated the absorbed doses in tumor cell nuclei, considering both self-radiation and cross-radiation from neighboring cells. A mathematical model of a spherical cell cluster (radius = 280 µm) was developed to simulate dose distribution, accounting for beta-particle range and linear energy transfer. Conclusions: Results indicate that the absorbed dose varies with cell position within the cluster, ranging from 3.2 Gy at the surface to 8.4 Gy at the center. The study also calculates cell survival probabilities using a linear-quadratic model, revealing a relative biological effectiveness (RBE) of up to 2 for [ 177 Lu] Lu-DOTATATE compared to gamma irradiation. These findings underscore the therapeutic potential of [ 177 Lu] Lu-DOTATATE in inducing tumor regression.