Targeted radiopharmaceuticals: an underexplored strategy for ovarian cancer

Ovarian cancer is the most common gynecological malignancy worldwide with the highest mortality. This low survival rate can be attributed to the fact that symptoms arise only at an advanced disease stage, characterized by a (micro)metastatic spread across the peritoneal cavity. Radiopharmaceuticals, composed of a targeting moiety coupled with either a diagnostic or therapeutic radionuclide, constitute a relatively underexplored theranostic approach that may improve the current standard of care. Efficient patient stratification, follow-up and treatment are several caveats that could be addressed with theranostics to improve patient outcomes. So far, the bulk of research is situated and often halted at the preclinical level, employing murine models of primary and metastatic peritoneal disease that do not necessarily provide an accurate representation of the disease heterogeneity, (intrinsic) drug resistance or the complex physiological interactions with the tumor microenvironment. Radioimmunoconjugates with therapeutic α- and electron-emitting radionuclides have been the prevailing standard, targeting a myriad of cell-membrane markers that are expressed in the various heterogeneous histological subtypes of ovarian cancer. Evidently, several hurdles exist within preclinical research that are potentially withholding these agents from advancing into clinical practice. On the other hand, the field of nuclear medicine has also seen significant innovation to address shortcomings related to target/ligand identification, preclinical research models, radiochemistry, radiopharmacy and dosimetry, as outlined in this review. Altogether, theranostics hold great promise to answer an unmet medical need for ovarian cancer.