Theranostics for Well and Moderately Differentiated GEP-NEN

Abstract

Neuroendocrine neoplasms (NEN) are rare, heterogeneous, and typically slowly growing tumours. The most common location is the gastro-entero-pancreatic system (GEP-NEN). NENs are classified according to their proliferative activity (Ki-67 index, G1-3). In this context, well-differentiated tumours typically express somatostatin receptors (SSTR), thus serving as targets for nuclear medicine theranostics. In this approach, diagnostic molecular imaging, usually by positron emission tomography/computed tomography (PET/CT), can be followed by individually tailored peptide radioreceptor therapy (PRRT) with a β-emitter labeled radiopharmaceutical. In meta-analyses, diagnostics using SSTR-directed PET/CT showed a sensitivity of 93% and a specificity of 96%. SSTR-directed diagnostics can also be used to trace tumours in-vivo, enabling radioguided surgery. The decision to initiate PRRT should always be made in an interdisciplinary tumour conference and tumour progression during previous therapy should be documented. This treatment is administered intravenously for 4 times at 8-week intervals in specialised nuclear medicine centres. PRRT efficacy was prospectively evaluated in the NETTER-1 study and demonstrated a significant improvement in progression-free survival (primary endpoint). Based on these results, Lutathera (177Lu-DOTATATE) is now available as a radiopharmaceutical approved in Germany for the treatment of non-resectable or metastatic or progressive, well-differentiated (G1 and G2), SSTR-positive GEP-NEN.