Dotatate is a synthetic peptide used in nuclear medicine, designed to mimic the natural hormone somatostatin. It is a DOTA-conjugated peptide, meaning its chemical structure allows it to be easily attached to radioactive isotopes. This design enables it to interact with specific biological targets, making it useful in medical diagnostics and treatment.
The Target of Dotatate
Dotatate is engineered to locate and bind to somatostatin receptors (SSTRs), proteins found on the surface of certain cells. There are five known subtypes, with somatostatin receptor subtype 2 (SSTR2) being particularly relevant due to its high expression in specific tumor types. Neuroendocrine tumors (NETs) frequently display a higher number of these receptors on their cell surfaces compared to healthy tissues. This overexpression of SSTRs, especially SSTR2, allows dotatate to specifically target these cancerous cells.
The presence of SSTR2 in NETs, including those originating in the digestive system, lungs, and pancreas, makes them susceptible to dotatate-based approaches. Other tumors, such as pheochromocytomas and paragangliomas, also express a high density of somatostatin receptors, making them additional targets. This selective binding allows for precise identification and treatment delivery to these cancer cells, distinguishing dotatate from therapies that might affect a broader range of cells.
Dotatate for Medical Imaging
For diagnostic imaging, dotatate is combined with a radioactive isotope, most commonly Gallium-68 (Ga-68), to create Ga-68 DOTATATE. This compound is administered intravenously. Once injected, Ga-68 DOTATATE circulates and attaches to the somatostatin receptors abundantly present on neuroendocrine tumor cells.
A Positron Emission Tomography/Computed Tomography (PET/CT) scanner detects the gamma radiation emitted by the decaying Gallium-68. The PET component provides functional information, showing where the tracer has accumulated and indicating tumor locations. The CT component provides detailed anatomical images, allowing doctors to pinpoint tumor size, location, and spread. This combination of functional and anatomical data aids in accurate staging, treatment planning, and monitoring therapy effectiveness.
Dotatate for Cancer Treatment
Dotatate can also be used for cancer treatment by attaching it to a different radioactive particle, Lutetium-177 (Lu-177), forming Lutetium Lu 177 dotatate, known as Lutathera. This therapeutic approach is called Peptide Receptor Radionuclide Therapy (PRRT). When Lu-177 DOTATATE is administered intravenously, it travels through the bloodstream and binds to the same somatostatin receptors on neuroendocrine tumor cells targeted during imaging.
Upon binding, radioactive Lu-177 is internalized by tumor cells, delivering a localized dose of beta radiation directly to them. The beta particles have a short tissue penetration range, typically up to 2 millimeters, allowing concentrated radiation delivery to the tumor while minimizing damage to surrounding healthy tissues. This targeted radiation induces DNA damage within cancer cells, leading to their death and inhibiting tumor growth. PRRT with Lu-177 DOTATATE is a treatment, primarily for patients with advanced or spreading neuroendocrine tumors, including gastroenteropancreatic NETs, that are somatostatin receptor-positive.
The Patient Experience
Patients undergoing a DOTATATE scan or PRRT treatment can expect specific procedural steps and preparations. For a Ga-68 DOTATATE scan, preparation typically involves fasting for a few hours. Patients may also be advised to temporarily stop certain somatostatin analog medications, such as short-acting octreotide, for at least 24 hours before the scan to ensure optimal tracer uptake. Long-acting somatostatin analogs like Octreotide LAR or Lanreotide might need to be paused for 1 to 2 days, often scheduling the scan just before the next injection.
The procedure begins with an intravenous injection of the Ga-68 DOTATATE tracer into a vein. After injection, a waiting period of 45 minutes to an hour allows the tracer to circulate and bind to tumor cells. The patient then lies on a table that moves into the PET/CT scanner, where imaging usually takes 25 to 60 minutes, depending on the area scanned. Following the scan, patients are advised to drink plenty of fluids to help flush the remaining tracer from their system.
For Lu-177 DOTATATE (PRRT) treatment, preparation is more involved, including a longer withdrawal period for long-acting somatostatin analogs, often 4 to 6 weeks. Short-acting versions can be used until 24 hours before treatment. To protect kidneys from radiation, patients receive an intravenous infusion of an amino acid solution, typically containing arginine and lysine, starting 30 to 60 minutes before the Lu-177 DOTATATE infusion and continuing for several hours. The Lu-177 DOTATATE is administered intravenously over several hours, and anti-nausea medication is given. Patients are monitored during and after infusion, and temporary radiation precautions are advised to limit exposure to others.