Gastroenteropancreatic neuroendocrine tumours (GEP-NETs) are a rare group of malignancies that have shown an increased global burden over the recent decades with an incidence of 3.56 per 1,00,000 persons. The 2017 WHO classification categorized pancreatic neuroendocrine neoplasms (NENs) into two broad types: well-differentiated pancreatic NEN, also referred as neuroendocrine tumour (NET) and poorly-differentiated NEN, otherwise known as neuroendocrine carcinoma (NEC). NETs were further subcategorized into grades depending on the Ki-67 proliferation index and mitotic index: G1 (Ki-67 index < 3% and mitotic index < 2/10 high-power fields); G2 (Ki-67 index 3-20 % and mitotic index 2-20/10 high-power fields); and G3 (Ki-67 index > 20% and mitotic index > 20/10 high-power fields).

Most of the NETs progress slowly over the years, however, the aggressiveness varies according to the primary site. While small intestinal NETs tend to progress indolently in the metastatic setting, gastric and rectal NETs often have a rapid progression once they become metastatic. Treatment options for advanced inoperable or metastatic GEP-NETs are currently limited. While somatostatin analogues viz. octreotide and lanreotide are widely used as first-line treatment for advanced GEP-NETs, targeted and cytotoxic chemotherapy are reserved for progressive disease. However, more often than not, disease progression eventually ensues and there exists a lack of therapeutic alternatives. Further, the adverse effects and costs associated with these treatment modalities often limit their practical utility for patients especially in low to middle income countries. In this setting, Peptide Receptor Radionuclide Therapy (PRRT) offers an attractive option with encouraging results over several retrospective and prospective studies.

Increased somatostatin receptor (SSTR) expression in NETs as demonstrated by high-grade uptake on SSTR scintigraphy provides the rationale for the use of PRRT in NETs, especially G1 and G2. The PRRT agents consist of a radionuclide (⁹⁰Y-Yttrium 90 or ¹⁷⁷Lu-Lutetium 177) linked to a peptide (SSTR agonist either TOC-Tyr3 Octreotide or TATE-Tyr3Octreotate or TATE ) by means of a chelator (DOTA). The binding of the agents to the SSTRs on the tumour cell membrane enables the delivery of the beta emitting radionuclides, thereby leading to cellular damage. Of the PRRTs, ¹⁷⁷Lu-DOTATATE is the only FDA approved agent for advanced/unresectable GEP-NETs. The approval was based on the NETTER-1 trial comprising 229 patients with progressive, well-differentiated, locally advanced/inoperable or metastatic SSTR positive mid gut NET.