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Therapeutic radiopharmaceuticals are labeled with either beta- or alpha-emitting isotopes. The tissue penetration of these isotopes is inversely proportional to their linear energy transfer (LET). Beta-emitting radioisotopes, e.g., Yttrium-90 (90Y) and Lutetium-177 (177Lu), have a low LET and an indirect cytocidal effect on tumor cells, primarily by ionizing reactive oxygen species that cause mostly single-strand DNA damage. On the other hand, alpha-emitting radioisotopes (e.g., Radium-223 and Actinium-225) have a high LET across a short distance (a few cell diameters). As such, they deposit a large amount of energy from their nucleus and cause irreversible damage to target cells, while collateral damage to the surrounding healthy tissue remains minimal (Mango L. 2017).

Exploration of theranostics with beta-emitting radiopharmaceuticals.

Targeted radionuclide therapy (TRT) involves the systemic administration of a high dose of radiopharmaceuticals (several gigabecquerels). Unlike external beam radiation, where a homogenous radiation dose is delivered to the tumor area, TRT delivers a heterogenous radiation dose within tumors at a steady but low absorbed rate (Kerr CP et al. 2022).

Ilustration of targeted radiopharmaceuticals delivering precision therapy.


  • Mango, L. 2017. “Theranostics: A Unique Concept to Nuclear Medicine.” Archives of Cancer Science and Therapy 1(1): 001–004.
    DOI: 10.29328/journal.acst.1001001

  • Kerr, Caroline P. et al. 2023. “Developments in Combining Targeted Radionuclide Therapies and Immunotherapies for Cancer Treatment.” Pharmaceutics 15(1): 128. DOI: 10.3390/pharmaceutics15010128