Theragnostic radionuclides: a clinical perspective

The concept of theragnostics goes back to the earliest days of nuclear medicine, with [¹²³I/¹³¹I]iodide in thyroid disease and [¹²³I/¹³¹I]MIBG in phaeochromocytoma being examples in long-term use. However, in recent years there has been a great expansion in the application of theragnostics, beginning with [⁶⁸Ga/¹⁷⁷Lu]-labelled somatostatin peptides for evaluation and treatment of neuroendocrine tumors. We are currently seeing the rapid development of [⁶⁸Ga/¹⁷⁷Lu]PSMA theragnostics in metastatic prostate cancer. While these applications are very promising, there are a number of practicalities which must be addressed in the development and introduction of novel theragnostics. The physical half-lives of the diagnostic and therapeutic radionuclides must be appropriate for imaging and delivery of targeted cell killing, respectively. The types of radioactive emissions are critical; beta particles can traverse several millimeters but also risk damaging non-target tissues, while alpha particles deliver their energy over a much shorter path length, a few cell diameters, and must be more directly targeted. It must be practical to produce the therapeutic radionuclide and the final radiopharmaceutical and deliver them to the final user within an appropriate time-frame determined by half-life and stability. The biodistribution of the agent must demonstrate adequate accumulation and retention in the target tissue with clearance from adjacent and/or radio-sensitive normal tissues. The commercial success of recently introduced theragnostics suggests a rosy future for personalized medicine.