PhD Defense | Michelle Andersson | Modeling of kidney absorbed dose heterogeneity and toxicity in radiopharmaceutical therapy with Tb-161 and Lu-177 radiolabeled peptides.

Modeling of kidney absorbed dose heterogeneity and toxicity in radiopharmaceutical therapy with ¹⁶¹Tb and ¹⁷⁷Lu radiolabeled peptides

Radiopharmaceutical therapy is designed to target and destroy cancer cells while sparing healthy tissue. However, the kidneys are a main organ at risk due to them filtering and reabsorbing many radiopharmaceuticals, leading to irradiation of kidney tissues which may cause radiation-induced nephrotoxicity. In order to optimize current and future radiopharmaceutical treatments, improved understanding of effects on the kidney to irradiation in radiopharmaceutical therapy is of great interest.

This PhD project developed a computational kidney model to study radiation dose at the microscopic level of individual nephron substructures. Using this model, differences in radiation dose and biological effects between two clinically relevant radionuclides, lutetium-177 (¹⁷⁷Lu) and terbium-161 (¹⁶¹Tb), were evaluated in preclinical studies. The findings showed that ¹⁶¹Tb delivers higher radiation doses to certain kidney regions, which may increase the risk of injury.

By combining the experimental findings with mechanistic modeling, the work provides a framework for better predicting and comparing kidney toxicity in radiopharmaceutical therapy. These insights can support the safe clinical introduction of new therapeutic radionuclides, such as ¹⁶¹Tb.

Promoter:

• Nick Reynaert (ULB) 

SCK CEN mentor:

• Clarita Saldarriaga Vargas