Toward Personalized Radiopharmaceutical Therapy: Radiobiologic Insights Compared with External-Beam Radiotherapy.

Penninckx, Sébastien; Delbart, Wendy; Mileva, Magdalena; Kassas, Mutaz; Levillain, Hugo; Artigas, Carlos; Flamen, Patrick; Karfis, Ioannis · J Nucl Med · 2026

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Abstract

Radiopharmaceutical therapy differs from external-beam radiation therapy through systemic delivery, a heterogeneous dose distribution, and a low dose rate, challenging conventional radiobiology and dose-effect relationships. These features complicate dose constraints and support dosimetry-guided strategies. Integrating personalized dosimetry into clinical trials is key to optimizing efficacy and limiting toxicity. We emphasize the need for radiopharmaceutical therapy-specific models and trial designs incorporating spatial heterogeneity, radiosensitivity, and patient-specific factors to improve the therapeutic index.