Presentation on theme: "Receptor-guided tumor targeting for localization, staging and treatment."— Presentation transcript:
Receptor-guided tumor targeting for localization, staging and treatment
Neuroendocrine cells are part of the endocrine system ◦ a network of glands in the body that produce hormones and send them into the bloodstream to affect the function of different organs in the body. Neuroendocrine tumors are rare, and often cause excess hormone production. Metastases can grow large because they frequently grow slowly. Tumors occur most commonly in the digestive system but can occur in other parts of the body. They can be either: ◦ Non-Cancerous (benign) or ◦ Cancerous (malignant). ◦ Functioning produce hormones ◦ Non-Functioning not produce hormones
Neuroendocrine tumors over-express somatostatin receptors in their membranes. Octreotide is an analogue whose molecule is a shortened version of somatostatin's with a high affinity for these receptors. The radiolabeled form of octreotide is able to be imaged in scans (OctreoScan) and, therefore, pathological conditions overexpressing somatostatin receptors are easily recognized in this technique. Specifically, in the case of the detection of carcinoid tumors, OctreoScan has sensitivity nearly to 90 percent.
A receptor is a protein molecule, embedded in either the plasma membrane or cytoplasm of a cell, to which a mobile signaling (or "signal") molecule may attach. A molecule which binds to a receptor is called a "ligand," and may be a peptide (such as a neurotransmitter), a hormone, a pharmaceutical drug, or a toxin. When such binding occurs, the receptor goes into a conformational change which ordinarily initiates a cellular response.
Many hormone and neurotransmitter receptors are transmembrane proteins: transmembrane receptors are embedded in the phospholipid bilayer of cell membranes, these allow the activation of signal transduction pathways in response to the activation by the binding molecule, or ligand. E=extracellular space; I=intracellular space; P=plasma membrane
Most carcinoid tumors (carcinoid), are found in the appendix or the small intestine. Less commonly, they may arise in the lung or the pancreas. Rarely, they may arise in other parts of the body. Carcinoid tumors often grow slowly and it may be several years before any symptoms appear and the tumor is diagnosed. Men and women are affected equally. Usually found in adults over the age of 30. The exact cause is unknown.
Overproduction of serotonin and other hormones produce carcinoid syndrome. Symptoms include diarrhea flushing of the skin wheezing (similar to asthma) loss of appetite weight loss
Urine test A 24-hour urine collection is used to check whether there are raised levels of serotonin. X-rays and scans Chest x-ray Ultrasound scan CT scan MRI scan Nuclear Imaging Hot spots indicate the presence of high-affinity somatostatin receptors, which are located on most tumoral endocrine cells Also dependant on the density of receptors Octreotide scan 123MIBG scan Biopsy
Whole body imaging - requires expression of somatostatin receptors ◦ Localizes tumors and metastases ◦ Staging the spread of malignancy Therapy - requires expression of somatostatin receptors ◦ Determines potential for Octreotide and/or nuclear therapy ◦ Five subsets of somatostatin receptors ◦ Some tumors do not express somatostatin receptors
Indium In-111 Pentetreotide dose ◦ planar imaging - 111 MBq (3.0 mCi) ◦ SPECT imaging - 222 MBq (6.0 mCi) LFOV Medium Energy Imaging ◦ Planar – 500 K counts or 15 minutes/image Isolate the abdomen and chest from the liver ◦ Whole Body – 10 cm/minute or longer (30 minute head to pelvis) ◦ SPECT Image at 4 hours (whole-body or planar), 24 hours (whole-body or planar plus SPECT of abdomen), 48 hours (same) and 72 hours if necessary
Patient preparation ◦ Identify patient, verify doctor’s orders, explain the procedure. ◦ Have patient eat a full breakfast before injection, and to hydrate well before and after the injection. ◦ No solid intake (fast) until after 4 hour image. ◦ A mild laxative may be considered for the evening before the injection and continued for subsequent imaging.
Surgery Chemotherapy Interferon Radiotherapy Nuclear Medicine Therapy ◦ 131-MIBG( I-131-m-Iodine-benzyl-guanidine ) Similar to hormones that bind to neuroendocrine receptors ◦ Radio-labeled Octreotide Yttrium 90 177 Lutetium-DOTA0,Tyr3octreotate ( 177 Lu-DOTATATE), Somatostatin analogues (such as Octreotide) ◦ reduces the production of hormones by the tumor
metaiodobenzylguanidine or mIBG, is a radiopharmaceutical. It is a radiolabeled molecule similar to norepinephrine. Norepinephrine or noradrenaline is a catecholamine with dual roles as a hormone and a neurotransmitter. Catecholamines are "fight-or-flight" hormones that are released by the adrenal glands in response to stress. They are part of the sympathetic nervous system.
Dose: 3.3 – 4.1 GBq (89.0 – 110.8 mCi) 131I- MIBG 10 ml is mixed with 90 ml of 5% glucose infusion and the total volume of 100 ml is administered slowly (2-4 hours ) Images are usually taken at 24, 48, 72 and 96 hours post administration.
Named after cells where they develop: Insulinomas ◦ occur in any part of the pancreas – sugar levels Gastrinomas ◦ often start in the pancreas or the upper part of the small bowel (duodenum). ◦ produce too much of the hormone gastrin -too much gastric acid is produced Glucagonomas ◦ occur most often in the pancreas ◦ too much of the hormone glucagon - sugar levels VIPomas ◦ usually occur in the pancreas ◦ too much of a substance called vasoactive intestinal peptide. Somatostatinomas. ◦ rare ◦ occur in the pancreas, duodenum or jejunum (parts of the small intestine).
Surgery Chemotherapy Interferon Radiotherapy Nuclear Medicine Therapy 131MIBG Radio-labelled octreotide (Yittrium 90) Somatostatin analogues (such as octreotide) reduce the production of hormones by the tumor