Applications of 211At and 223Ra in targeted alpha-particle radiotherapy

Abstract

Targeted radiotherapy using agents tagged with α-emitting radionuclides is gaining traction with several clinical trials already undertaken or ongoing, and others in the advanced planning stage. The most commonly used α-emitting radionuclides are 213Bi, 211At, 223Ra and 225Ac. While each one of these has pros and cons, it can be argued that 211At probably is the most versatile based on its half life, decay scheme and chemistry. On the other hand, for targeting bone metastases, 223Ra is the ideal radionuclide because simple cationic radium can be used for this purpose. In this review, we will discuss the recent developments taken place in the application of 211At-labeled radiopharmaceuticals and give an overview of the current status of 223Ra for targeted α-particle radiotherapy.

Fig. (1)

Clonogenic survival of A431 human epidermoid carcinoma cells after exposure for 4 h to varying activity concentrations of [²¹¹At]SAGMB-MRT (open diamonds) and [²¹¹At]astatide (closed squares). Confidence interval lines for [²¹¹At]SAGMB-MRT are not quite visible as they are very close to the regression line.

Fig. (2)

Percentage of athymic rats with MCF-7/HER2-18 breast carcinoma carcinomatous meningitis surviving after intrathecal administration of 46 (dashed line) or 92 μCi (solid line) ²¹¹At-labeled trastuzumab or saline (dotted line) 3 days after intrathecal injection of 5×10⁶ tumor cells.

Fig. (3)

Percentage of athymic rats with MCF-7/HER2-18 breast carcinoma carcinomatous meningitis surviving after intrathecal administration of 28 μCi ²¹¹At-labeled trastuzumab (solid line), 30 μCi ²¹¹At-labeled TPS3.2 control mAb (dashed line) or saline 3 (dotted line) days after intrathecal injection of 5×10⁶ tumor cells.

Fig. (4)

Decay scheme for Radium-223.