Realistic multi-cellular dosimetry for ¹⁷⁷Lu-labelled antibodies: model and application

Area of Science:

• Medical Physics
• Radiopharmaceutical Therapy
• Cell Biology

Background:

• Preclinical dosimetric models often oversimplify absorbed dose distribution in vitro.
• Clonogenic survival is frequently reported by activity, not absorbed dose, limiting therapeutic assessment.

Purpose of the Study:

• To develop a multi-cellular dosimetry model for accurate absorbed dose calculation in clonogenic assays.
• To establish survival curves as a function of absorbed dose for targeted radionuclide therapy.

Main Methods:

• Generated realistic 3D cell culture geometries using general-purpose software.
• Implemented a hybrid Monte Carlo and analytical approach for dosimetry calculations.
• Applied the model to compare Betalutin®, 177Lu-rituximab, and 177Lu-Erbitux efficacy on B cells.

Main Results:

• The 3D cellular model provides a more accurate assessment of absorbed dose distribution.
• Enabled better understanding of cellular death mechanisms in targeted radionuclide therapy.
• Demonstrated the model's applicability to various radiopharmaceuticals and cell distributions.

Conclusions:

• The developed multi-cellular dosimetry model enhances the accuracy of in vitro clonogenic assays.
• Facilitates precise survival curve establishment based on absorbed dose.
• Offers a versatile tool for evaluating targeted radionuclide therapies and radiopharmaceuticals.