A somatostatin receptor is a protein on the surface of many cells that functions as a docking station for the hormone somatostatin. When somatostatin binds to its receptor, it triggers a specific response inside the cell, allowing different parts of the body to communicate. The presence and number of these receptors can vary significantly between cell types. This allows somatostatin to have a wide range of effects depending on where it is acting.
The Role of Somatostatin and its Receptors
The primary function of the somatostatin and receptor system is inhibitory, acting as a brake on various cellular processes. In the endocrine system, it regulates hormone production. For instance, it slows the pituitary gland’s release of growth hormone and curbs the secretion of insulin and glucagon in the pancreas, keeping growth and blood sugar levels stable.
Beyond hormone regulation, this system helps moderate digestion by slowing stomach emptying, reducing intestinal contractions, and decreasing the release of digestive fluids. These diverse effects are possible because there are five distinct receptor subtypes, SSTR1 through SSTR5. Different tissues express different combinations of these subtypes, allowing for a tailored physiological response.
Connection to Neuroendocrine Tumors
The link between somatostatin receptors and cancer is clear in neuroendocrine tumors (NETs), which arise from cells of the endocrine and nervous systems. A defining feature of many NETs is an unusually high number of somatostatin receptors on their surface, a phenomenon known as overexpression. This characteristic distinguishes NETs from healthy cells and many other types of cancer. While most NETs express multiple receptor subtypes, SSTR2 is the one most commonly and densely present, providing a unique feature for specialized diagnosis and treatment.
Diagnostic Imaging Applications
The overexpression of somatostatin receptors on NET cells is exploited for diagnostic imaging. This process uses a somatostatin analog, a molecule designed to mimic natural somatostatin, attached to a radioactive isotope. This compound, called a radiotracer, circulates through the blood and binds specifically to the abundant receptors on tumor cells.
The standard for this imaging is the Gallium-68 (Ga-68) DOTATATE PET/CT scan. The DOTATATE portion is the somatostatin analog targeting SSTR2 receptors, while Gallium-68 is the radioactive component. A Positron Emission Tomography (PET) scanner detects the signals from the Gallium-68, creating images that show the radiotracer’s location.
These PET images are fused with a computed tomography (CT) scan, which provides a detailed anatomical map. The combined PET/CT scan allows physicians to see precisely where tumors are located as they “light up” from the radiotracer. This technique is used for staging the disease and identifying if a patient’s tumors have enough receptors for targeted therapies.
Therapeutic Targeting
The same principle of targeting overexpressed somatostatin receptors is also applied for therapy. This approach uses the receptors as a gateway to affect the cancer cells.
Somatostatin Analogs (SSAs)
One method uses drugs called somatostatin analogs (SSAs), such as octreotide and lanreotide, which are stable, long-acting versions of somatostatin. When administered, these SSAs bind to receptors on the NET cells. This binding can block the tumor from releasing excess hormones, controlling symptoms like severe diarrhea or skin flushing. It can also have an antiproliferative effect, slowing or halting tumor growth to stabilize the disease.
Peptide Receptor Radionuclide Therapy (PRRT)
A more direct therapeutic strategy is Peptide Receptor Radionuclide Therapy (PRRT). This approach turns the somatostatin analog into a vehicle for delivering radiation directly to the cancer. A radioactive particle, like Lutetium-177 (Lu-177), is attached to a somatostatin analog such as DOTATATE. This radio-labeled molecule travels through the body and binds to the SSTR2 receptors on tumor cells. Once docked, the attached Lu-177 emits cell-damaging radiation over a very short distance, focusing its destructive power on the cancer while limiting damage to healthy tissues.