Pendetide
Pendetide is a synthetic peptide analog of somatostatin that is used in nuclear medicine imaging and therapy, primarily for the detection and treatment of neuroendocrine tumors (NETs). It is composed of a chain of amino acids coupled to a chelator, most commonly diethylenetriaminepentaacetic acid (DTPA), which allows it to be radiolabeled with various radionuclides, such as indium-111 (111In) for diagnostic imaging using scintigraphy or lutetium-177 (177Lu) for targeted radionuclide therapy (PRRT).
The mechanism of action relies on the high affinity of pendetide for somatostatin receptors (SSTRs), particularly subtypes 2 and 5, which are frequently overexpressed on the surface of neuroendocrine tumor cells. Once radiolabeled pendetide is administered intravenously, it binds to these receptors, allowing for visualization of tumor locations and size via gamma camera imaging or delivering a cytotoxic radiation dose directly to the tumor cells.
Diagnostic Use: 111In-pentetreotide scintigraphy (OctreoScan) is a common diagnostic application of pendetide. It provides whole-body imaging, enabling the detection of both primary and metastatic NET lesions.
Therapeutic Use: Lutetium-177-DOTATATE (Lutathera) is a peptide receptor radionuclide therapy (PRRT) that utilizes a DOTATATE conjugate, similar in principle to DTPA-pendetide but using a different chelator (DOTA), which is linked to the somatostatin analogue octreotate. 177Lu-DOTATATE, like 111In-pentetreotide, targets SSTRs on NET cells, but delivers a beta-emitting radionuclide (177Lu) to induce cell damage and tumor regression.
Pendetide and its related compounds, such as DOTATATE, offer targeted approaches for managing NETs, contributing to improved diagnostic accuracy and therapeutic outcomes. Potential side effects of treatment with radiolabeled pendetide include fatigue, nausea, vomiting, and hematological toxicity.