Theranostics with Somatostatin Receptor Antagonists

Abstract

AbstractSomatostatin receptors (SST), especially SST subtype 2 (SST2), are important targets for the management of patients with neuroendocrine tumours (NETs) or neuroendocrine neoplasias (NENs). Peptide receptor radionuclide therapy (PRRT) with 177Lu-labelled SST agonists, for example, 177Lu-DOTA-TOC or 177Lu-DOTA-TATE, is recommended by the European Neuroendocrine Tumour Society as second-line treatment after progression under treatment with somatostatin analogues in patients with metastatic, SST positive grade 1 and 2 midgut NETs. PET/CT imaging with 68Ga-labelled SST agonists, for example, 68Ga-DOTA-TOC or 68Ga-DOTA-TATE, plays an important role in staging and restaging NETs. Furthermore, SST PET/CT can identify those patients with highly 68Ga-DOTA-TOC or 68Ga-DOTA-TATE avid tumours. These are the patients who will benefit from PRRT. As a result, SST PET/CT can predict the treatment efficacy of 177Lu-DOTA-TOC or 177Lu-DOTA-TATE. This allows a personalized treatment approach, also called a therapeutic/diagnostic approach = theranostic approach. Until recently, it was thought that internalisation of the radiolabelled agonist was mandatory for SST-mediated imaging and therapy. It was Ginj et al. who proposed in 2006 the paradigm shift that radiolabelled SST antagonists may perform better than agonists despite lacking internalisation. In this chapter, the preclinical and clinical development, current status and possible future developments of radiolabelled SST antagonists are discussed.