New designs of octreotate analogues for improved imaging and therapy of neuroendocrine tumors

In 2019, the World Health Organization (WHO) classified cancer as the second cause of
mortality (after cardiovascular diseases) in 112 out of 183 countries worldwide [1].
Among all cancer types, the neuroendocrine neoplasms (NENs), constituted of the neuroendocrine
tumors (NETs) and neuroendocrine carcinomas (NECs), are rare tumors
originating from neuroendocrine cells, and they can occur in many different organs of
the body. NECs are representing 10-20% of all NENs. There are characterized as poorly
differentiated NENs. Neuroendocrine carcinomas (NECs) are classified as grade 3 (G3)
carcinomas. In contrast, neuroendocrine tumors (NETs) are well-differentiated. In 2022,
the WHO graded the NETs in three types: G1, G2, G3 [2]. Both tumor grade and disease
stage—assessed using the tumor-node-metastasis (TNM) staging system—serve as key
prognostic factors and play a critical role in guiding the disease management strategy.
The majority of NETs arise in the gastroenteropancreatic (GEP) tract or the lungs (50 –
70% and 20- 25 % of all NETs, respectively) (Figure 1). NETs can be functional or nonfunctional.
The functional NETs are characterized by the secretion of hormones, such as
serotonin or insulin causing some symptoms to the patient [3]. They are also slow-growing,
which often leads to delays in diagnosis, typically resulting in detection at a metastatic
stage. In general, NETs have tendency to metastasize to the liver and skeleton.
Therefore, for an efficient therapy, it is important to evaluate tumor staging precisely.
NETs also share similarities, such as the expression of specific neuroendocrine markers
(e.g. chromogranin A and synaptophysin). Furthermore, NETs frequently overexpress
somatostatin receptors (SSTRs).