Theragnostics in primary and secondary liver tumors: the need for a personalized approach

Primary and secondary hepatic tumors have a dramatic impact in oncology. Despite many advances in diagnosis and therapy, the management of hepatic malignancies is still challenging, ranging from various loco-regional approaches to system therapies. In this scenario, theragnostic approaches, based on the administration of a radiopharmaceuticals' pair, the first labeled with a radionuclide suitable for the diagnostic phase and the second one bound to radionuclide emitting particles for therapy, is gaining more and more importance. Selective internal radiation therapy (SIRT) with microspheres labeled with ⁹⁰Y or ¹⁶⁶Ho is widely used as a loco-regional treatment for primary and secondary hepatic tumors. While ¹⁶⁶Ho presents both gamma and beta emission and can be therefore considered a real "theragnostic" agent, for ⁹⁰Y-microspheres theragnostic approach is realized at the diagnostic phase through the utilization of macroaggregates of human albumin, labeled with ^99mTc as "biosimilar" agent respect to microspheres. The aim of the present review was to cover theragnostic applications of ⁹⁰Y/¹⁶⁶Ho-labeled microspheres in clinical practice. Furthermore, we report the preliminary data concerning the potential role of some emerging theragnostic biomarkers for hepatocellular carcinoma, such as glypican-3 (GPC3) and prostate specific membrane antigen (PSMA).