Lutetium Lu 177 dotatate

Somatostatin receptors (SSRT) are inhibitory G-protein coupled receptors that are ubiquitously expressed in normal and cancer cells. The natural ligand of SSRTs, somatostatin, is a potent inhibitory regulator of pituitary and gastrointestinal hormone release and proliferation. Advanced and well-differentiated neuroendocrine tumors express high levels of somatostatin receptors, especially somatostatin recetor type 2 (SSRT2), and have the ability to incorporate amines intracellularly and decarboxylate them.

As an analogue of somatostatin, Lutetium Lu 177 dotatate binds to somatostatin receptor with highest binding affinity for SSRT2. Upon binding to SSRT-expressing cells, including malignant somatostatin receptor-positive tumors, the radiolabelled compound is internalized and the beta emission from the radioligand Lu 177 induces cellular damage by formation of free radicals in somatostatin receptor-positive cells and in neighboring cells. As with other somatostatin analogues, Lu177 dotatate is expected to suppress excessive secretion of amines and hormones, such as serotonin, from carcinoid tumors and certain types of endocrine pancreatic tumors (glucagonoma, VIPoma and gastrinoma). The release of peptides and other gastrointestinal hormones important in tumor growth, including gastrin, cholecystokinin and epidermal growth factor (EGF), may also be reduced through promoted somtatostatin signalling pathways.