Normal Tissue Dosimetry of Intraperitoneal ²²⁴Ra Microparticle Therapy: Data from First-in-Human Studies in Patients with Peritoneal Metastases.

Abstract

Two early-phase clinical studies evaluated α-emitting ²²⁴Ra adsorbed to calcium carbonate microparticles ([²²⁴Ra]CaCO₃-MP). Patients with peritoneal metastases from ovarian or colorectal cancer underwent complete cytoreductive surgery 2 days before intraperitoneal injection of [²²⁴Ra]CaCO₃-MP. The aim of this work was to assess biodistribution and estimate absorbed doses to normal organs and tissues in a dosimetry cohort. <b>Methods:</b> Three patients with ovarian cancer and 6 patients with colorectal cancer were administered 7 MBq of [²²⁴Ra]CaCO₃-MP intraperitoneally. Blood was sampled at 5 time points. ²²⁴Ra and ²¹²Pb in blood were estimated by γ-counter measurements of photons originating from ²¹²Pb and its daughters. Biexponential curves fit to ²²⁴Ra and ²¹²Pb blood activities were combined with biokinetic models from International Commission of Radiation Protection (ICRP) publications 137 and 151 to estimate absorbed doses. γ-camera images were acquired to evaluate biodistribution. Additionally, a sensitivity analysis was performed to investigate the effect of deviation in ICRP transfer coefficients. <b>Results:</b> The highest absorbed dose was to the endosteal bone surface, receiving up to 0.85 Gy/7 MBq, followed by kidneys, liver, and red bone marrow receiving up to 0.35, 0.28 and 0.14 Gy/7 MBq, respectively. In the sensitivity analysis, the range was 0.18-2.0, 0.090-0.96, 0.083-0.62, and 0.042-0.31 Gy/7 MBq for the 4 organs, respectively. Besides radioactivity in the content of the large intestine at later time points, no visibly distinguishable uptake was assessed outside the peritoneal cavity on γ-camera images, supporting the modeling results. <b>Conclusion:</b> Based on biokinetic modeling combined with measured activity in patient blood samples, no patient received absorbed doses exceeding 0.85 Gy/7 MBq for any organ. Combined with clinical reports, and taking the potential range in absorbed doses given by the sensitivity analysis into account, the absorbed doses to the investigated tissue are likely below the relevant range of normal tissue complication probabilities for this treatment.