Future of theranostics: An outlook on precision oncology in nuclear medicine

Abstract

Molecular alterations in malignant disease result in the expression or upregulations of various targets that can be used for imaging and treatment with radiopharmaceuticals. This theranostic principle has acquired greater importance in personalized medicine in recent years, particularly in oncology, where advanced tumors can be treated effectively with low side effects. Since the pioneering use of 131I in differentiated thyroid cancer in the 1940s, remarkable achievements in nuclear medicine endoradiotherapy have been demonstrated, mainly in the treatment of neuroendocrine neoplasms by using 177Lu-labeled somatostatin analogs or in the treatment of advanced prostate cancer using prostate-specific membrane antigen-directed radionuclide therapy. Besides that, this review focuses on promising novel radiopharmaceuticals and describes their preclinical and clinical status. Radiolabeled antibodies, such as 131I-omburtamab directed against the B7-H3 protein on the surface of neuroblastoma cells; HuMab-5B1, a 89Zr/177Lu-labeled antibody for the treatment of CA19-9-expressing malignancies; and 177Lu-lilotomab, a CD37 antibody for the treatment of B-cell lymphomas, are being highlighted. The neurotensin receptor ligand 111In/177Lu-3B-227 has demonstrated high potential in imaging and therapy for several malignancies (e.g., pancreatic adenocarcinomas). Targeting of the fibroblast activation protein is currently being explored for different tumor entities using PET imaging with the fibroblast activation protein inhibitor (FAPI) 68Ga-FAPI-04, and the first therapeutic applications of 90Y-FAPI-04 have been applied. After 2 decades of rapid development in theranostics, a variety of new targets are available for further clinical investigation.