Theranostics in neuroendocrine tumors: an overview of current approaches and future challenges

Julie Refardt, Johannes Hofland, Antwi Kwadwo, Guillaume P. Nicolas, Christof Rottenburger, Melpomeni Fani, Damian Wild, Emanuel Christ*

*Corresponding author for this work

Research output: Contribution to journalReview articleAcademicpeer-review

28 Citations (Scopus)


Neuroendocrine neoplasms (NENs) comprise a heterogeneous group of tumors, mainly localized in the gastrointestinal system. What characterizes NENs is the expression of hormone receptors on the tumor cell surface, making them accessible for diagnostic and therapeutic approaches (theranostics) using radiolabelled peptides. Somatostatin receptors subtype-two (SST2) play an important role in NENs since they are overexpressed and homogeneously distributed at the surface of the majority of NENs. Accordingly, targeting SST2 for diagnostic and therapeutic purposes has been established. Current research aims at upregulating its expression by epigenetic treatment or improving its targeting via use of alternative radioligands. In addition, recent data suggest a future role of SST antagonists as a diagnostic tool and a potential therapeutic option. Another promising target is the glucagon-like peptide-1 (GLP-1) receptor. Targeting GLP-1R using exendin-4 (GLP-1 analogue) has a high sensitivity for the localization of the often SST2-negative sporadic insulinomas and insulinomas in the context of multiple endocrine neoplasia type-1. Further options for patients with insufficient expression of SST2 involve metaiodobenzylguanidine (MIBG) and the molecular target C-X-C motif chemokine receptor-4 (CXCR4), which have been evaluated for potential theranostic approach in symptomatic NENs or dedifferentiated tumors. Recently, new targets such as the glucose-dependent insulinotropic polypeptide receptor (GIPR) and the fibroblast activation protein (FAP) have been identified in NENs. Finally, minigastrin – a ligand targeting the cholecystokinin-2 (CCK2) receptors in medullary thyroid carcinoma and foregut neuroendocrine tumors – may improve future management of these diseases with currently limited therapeutic options. This review summarises the current approaches and future challenges of diagnostic and therapeutic evaluations in neuroendocrine neoplasms.

Original languageEnglish
Pages (from-to)581-594
Number of pages14
JournalReviews in Endocrine and Metabolic Disorders
Issue number3
Publication statusPublished - 3 Jun 2021

Bibliographical note

Funding Information:
JR is supported by a grant from the Swiss National Science Foundation (SNF-181720). The different studies for this review were supported by the Swiss National Science Foundation (grant number 320030_152938 to EC) and the Desirée and Niels Yde Foundation (grant number 389-12 to DW), which had no role in study design, data collection, analysis, interpretation or writing of the report.

Publisher Copyright:
© 2020, Springer Science+Business Media, LLC, part of Springer Nature.


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