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

Reviews in Endocrine and Metabolic Disorders volume 22, pages 581–594 (2021)Cite this article

Abstract

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.

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Affiliations

  1. Department of Internal Medicine, Section of Endocrinology, ENETS Center of Excellence, Erasmus Medical Center, Rotterdam, the Netherlands

    Julie Refardt & Johannes Hofland

  2. Department of Clinical Research, University of Basel, Basel, Switzerland

    Julie Refardt

  3. ENETS Center of Excellence for Neuroendocrine and Endocrine Tumors, University Hospital Basel, Basel, Switzerland

    Antwi Kwadwo, Guillaume P. Nicolas, Christof Rottenburger, Damian Wild & Emanuel Christ

  4. Division of Nuclear Medicine, University Hospital Basel, Basel, Switzerland

    Antwi Kwadwo, Guillaume P. Nicolas, Christof Rottenburger & Damian Wild

  5. Division of Radiopharmaceutical Chemistry, University Hospital Basel, Basel, Switzerland

    Melpomeni Fani

  6. Department of Endocrinology, Diabetology and Metabolism, University Hospital Basel, Basel, Switzerland

    Emanuel Christ

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  1. Julie Refardt
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  2. Johannes Hofland
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  3. Antwi Kwadwo
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  4. Guillaume P. Nicolas
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  5. Christof Rottenburger
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  6. Melpomeni Fani
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  7. Damian Wild
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  8. Emanuel Christ
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Corresponding author

Correspondence to Emanuel Christ.

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Disclosures

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.

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Refardt, J., Hofland, J., Kwadwo, A. et al. Theranostics in neuroendocrine tumors: an overview of current approaches and future challenges. Rev Endocr Metab Disord 22, 581–594 (2021). https://doi.org/10.1007/s11154-020-09552-x

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Keywords

  • Neuroendocrine neoplasms
  • Somatostatin receptors
  • GLP-1R-imaging
  • Minigastrin