1. Receptor-guided tumor targeting for localization, staging and treatment

2.  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

3.  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.

4.  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.

5.  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

6.  Carcinoid tumors  Gastroenteropancreatic tumors (GEPs)  Phaeochromocytoma  Neuroblastoma  Paraganglioma  Medullary thyroid carcinoma

7.  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.

9.  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

10.  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

11.  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

12.  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

13. 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.

15.  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

16.  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.

17.  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.

18. 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).

19.  X-rays and scans  Chest x-ray  Ultrasound scan  CT scan  MRI scan  Nuclear Medicine Imaging  Octreotide scan  123MIBG scan  PET (positron emission tomography) scan  Biopsy

20.  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

23. most often in the head and neck