Tumor Response to Radiopharmaceutical Therapies: The Knowns and the Unknowns

Abstract

Radiopharmaceutical therapy (RPT) is defined as the delivery of radioactive atoms to tumor-associated targets. In RPT, imaging is built into the mode of treatment since the radionuclides used in RPT often emit photons or can be imaged using a surrogate. Such imaging may be used to estimate tumor-absorbed dose. We examine and try to elucidate those factors that impact the absorbed dose-versus-response relationship for RPT agents. These include the role of inflammation- or immune-mediated effects, the significance of theranostic imaging, radiobiology, differences in dosimetry methods, pharmacokinetic differences across patients, and the impact of tumor hypoxia on response to RPT.

Keywords: dosimetry; imaging; radionuclide therapy; radiopharmaceutical therapy; radiopharmaceuticals; theranostics.

FIGURE 1.

Tumor dose–response relationship in PRRT for 13 patients treated with ⁹⁰Y-DOTATOC (A) and 24 patients treated with ¹⁷⁷Lu-DOTATATE (B). (Adapted from Pauwels et al. ( 102 ) and Ilan et al. ( 103 ).)