OctreoscanOctreoscan

Radiolabled Somatostatin AnalogRadiolabled Somatostatin Analog

What Is Somatostatin?What Is Somatostatin?

Somatostatin is a naturally occurring Somatostatin is a naturally occurring neuropeptide found in the hypothalamus neuropeptide found in the hypothalamus that possesses a wide range of that possesses a wide range of pharmacological properties, including pharmacological properties, including inhibition of growth hormone release and the inhibition of growth hormone release and the suppression of insulin and glucagon suppression of insulin and glucagon secretion. In its relationship to these secretion. In its relationship to these hormones it is similar to the feedback loop hormones it is similar to the feedback loop associated with thyroids and adrenals.associated with thyroids and adrenals.

Peptide BiodistributionPeptide Biodistribution

They are not monoclonal antibodiesThey are not monoclonal antibodies However, they behave in the same manner However, they behave in the same manner The peptide forms a lock and key The peptide forms a lock and key

relationship with receptors on a tumor cellrelationship with receptors on a tumor cell The ability to detect tumors depends on the The ability to detect tumors depends on the

specificity of the peptide to the receptors on specificity of the peptide to the receptors on the tumorthe tumor

Somatostatin ReceptorsSomatostatin Receptors

Somatostatin receptors have been demonstrated in Somatostatin receptors have been demonstrated in endocrine cells throughout the body, as well as in endocrine cells throughout the body, as well as in numerous endocrine tumors.numerous endocrine tumors.

Majority of neuroendocrine tumors, including carcinoids, Majority of neuroendocrine tumors, including carcinoids, islet cell carcinomas, and growth hormone producing islet cell carcinomas, and growth hormone producing pituitary adenomas have pituitary adenomas have cell membrane receptorscell membrane receptors with a with a high affinity for somatostatinhigh affinity for somatostatin

Somatostatin has also shown to inhibit Somatostatin has also shown to inhibit excessive excessive production of hormonesproduction of hormones caused by a variety of caused by a variety of neuroendocrine tumors, including carcinoids, vipomas neuroendocrine tumors, including carcinoids, vipomas (pancreatic tumor), gastrinomas, and insulinomas.(pancreatic tumor), gastrinomas, and insulinomas.

Somatostatin Receptors (Cont.)Somatostatin Receptors (Cont.)

Indications are for neuroendocrine tumorsIndications are for neuroendocrine tumors– Localizes in tumors with somatostatin receptors and are:Localizes in tumors with somatostatin receptors and are:

MeningiomaMeningioma Insulinoma InsulinomaPheochromocytomaPheochromocytoma Gastrinoma GastrinomaNeuroblastomaNeuroblastoma Paraganglioma ParagangliomaIslet cell carcinomaIslet cell carcinoma Pituitary adenoma Pituitary adenomaGlucagonomaGlucagonoma VIPoma VIPomaSmall cell lung carcinomaSmall cell lung carcinoma Carcinoid Carcinoid

Medullary thyroid carcinomaMedullary thyroid carcinoma

Peptides - OctreotidePeptides - Octreotide

Other tumors also possess similar binding sites:Other tumors also possess similar binding sites: MeningiomasMeningiomas Breast carcinomaBreast carcinoma AstrocytomasAstrocytomas Small cell carcinoma of the lungSmall cell carcinoma of the lung

Ability to Detect DiseaseAbility to Detect Disease

Disease Scintigraphy In vitro

Medullary thyroid carcinoma 20/28 71% 10/26 38%

Pheochromocytoma 12/14 86% 38/52 73%

Carcinoid 69/72 96% 54/62 88%

Small cell lung cancer 34/34 100% 4/7 57%

Non-small cell lung cancer 36/36 100% 0/17 0%

Meningiomas 14/14 100% 54/55 98%

Breast cancer 37/50 74% 33/72 46%

Non-Hodgkin's Lymphoma 59/74 80% 0/17 0%

Hodgkin's disease 23/24 96% 2/2 100%

PeptidesPeptides

In 1994 the FDA approved the first In 1994 the FDA approved the first

radiolabeled peptide for diagnostic imaging:radiolabeled peptide for diagnostic imaging:

111111In PentetreotideIn Pentetreotide or (OctreoScanor (OctreoScan

111In DTPA-d-Phe-octreotide

Peptide BiodistributionPeptide Biodistribution

They are not monoclonal antibodiesThey are not monoclonal antibodies However, they behave in the same manner However, they behave in the same manner The peptide forms a lock and key The peptide forms a lock and key

relationship with receptors on a tumor cellrelationship with receptors on a tumor cell The ability to detect tumors depends on the The ability to detect tumors depends on the

specificity of the peptide to the receptors on specificity of the peptide to the receptors on the tumorthe tumor

Human – Synthetic Human – Synthetic

Octreotide is a synthetic peptide developed from Somatostatin•The human form of stomatostatin is composed of 14 amino acids•Octreotide only has 8 amino acids, however, it behaves just like its human counter part•Being smaller, it clears faster and has improved target to background

Labeled OctreotideLabeled Octreotide

Octreotide is labeled via Octreotide is labeled via DTPA to In111DTPA to In111

Indium 111 pentreotide Indium 111 pentreotide (Octreoscan) is a (Octreoscan) is a radiolabeled analog of radiolabeled analog of somatostatin indicated for somatostatin indicated for the scintigraphic the scintigraphic localization of localization of neuroendocrine tumors neuroendocrine tumors bearing somatostatin bearing somatostatin receptors.receptors.

IndicationsIndications

Primary and Primary and metastatic metastatic neuroendocrine neuroendocrine tumorstumors– GH & TSH producing GH & TSH producing

pituitary tumorspituitary tumors– ParagangliomasParagangliomas– Medullary thyroid CAMedullary thyroid CA– Small cell lung CASmall cell lung CA

As the first peptide As the first peptide imaging agents, imaging agents, Octreoscan goes Octreoscan goes beyond imaging tumor beyond imaging tumor anatomy, providing anatomy, providing valuable clinical valuable clinical information about information about tumor biochemistry.tumor biochemistry.

Method of LocalizationMethod of Localization

Following intravenous injection, In111 Following intravenous injection, In111 pentreotide binds to somatostatin receptors pentreotide binds to somatostatin receptors present in tissues throughout the body, present in tissues throughout the body, concentrating in tumors that contain a high concentrating in tumors that contain a high density of somatostatin receptorsdensity of somatostatin receptors

Precautions and Patient Precautions and Patient PreparationPreparation

Insulinoma patients should be treated with IV Insulinoma patients should be treated with IV glucose prior/during injectionglucose prior/during injection– Causes severe hypoglycemic reactionCauses severe hypoglycemic reaction

Patients should be well hydratedPatients should be well hydrated– Octreoscan is excreted primarily through the Octreoscan is excreted primarily through the

kidneys, hydration will enhance renal clearance kidneys, hydration will enhance renal clearance thus reducing radiation exposurethus reducing radiation exposure

Bowel prep is warranted pre/post injectionBowel prep is warranted pre/post injection Octreotide acetate therapy should be Octreotide acetate therapy should be

suspended prior to Octreoscan administrationsuspended prior to Octreoscan administration

Precautions (Cont.)Precautions (Cont.)

Special Consideration - Insulinoma PatientsSpecial Consideration - Insulinoma Patients– Theoretically pentetreotide may decrease Theoretically pentetreotide may decrease

glucagon levels to the degree that insulin from glucagon levels to the degree that insulin from the tumor could significantly reduce blood the tumor could significantly reduce blood glucose levelsglucose levels

– Mallinckrodt recommends IV glucose solution Mallinckrodt recommends IV glucose solution be administered prior to and during be administered prior to and during OctreoScanOctreoScanadministration

Scan to Injection TimeScan to Injection Time

Imaging is performed either planar or Imaging is performed either planar or SPECT 4 to 24 hours after injection.SPECT 4 to 24 hours after injection.

Imaging can be done at 48 hours as a follow Imaging can be done at 48 hours as a follow up to differentiate between neuroendocrince up to differentiate between neuroendocrince tumor and normal bowel uptake.tumor and normal bowel uptake.

Radiopharmaceutical and DoseRadiopharmaceutical and Dose

In111 Chloride Pentreotide (Octreoscan)In111 Chloride Pentreotide (Octreoscan) Kit contains lypholized pentetreotide and 1.1 Kit contains lypholized pentetreotide and 1.1

ml of 3 mCi of In111 Chloride solutionml of 3 mCi of In111 Chloride solution Should be stored in refrigerator and used Should be stored in refrigerator and used

within 6 hours of preparationwithin 6 hours of preparation Dose is 3-6 mCiDose is 3-6 mCi

Peptides - OctreotidePeptides - Octreotide

Imaging Procedure has two considerationsImaging Procedure has two considerations– Planar Planar – SPECTSPECT

Views and Camera Set UpViews and Camera Set Up

Large field of view gamma camera Large field of view gamma camera SPECT, WB and Static Imaging can be SPECT, WB and Static Imaging can be

performedperformed Energy peaks at 20% windowEnergy peaks at 20% window

– 173 keV and 247 keV173 keV and 247 keV

Medium energy collimatorMedium energy collimator Anterior and PosteriorAnterior and Posterior

– Head, Chest, Abdomen, and PelvisHead, Chest, Abdomen, and Pelvis

Normal DistributionNormal Distribution

InterpretationInterpretation– Normal biodistributionNormal biodistribution

Pituitary glandPituitary gland SpleenSpleen Liver (especially in patients with Liver (especially in patients with renal clearance) renal clearance) KidneysKidneys Urinary bladderUrinary bladder Normal thyroid gland (minimally)Normal thyroid gland (minimally) Colon (depending on laxative effectiveness)Colon (depending on laxative effectiveness)

Normal DistributionNormal Distribution the kidneys and bladder

(the route of excretion) the liver (diffuse low

uptake) the spleen (marked

uptake) the pituitary gland

(modest) thyroid gland (modest) occasionally the large

bowel at 24 hours.

http://www.med.harvard.edu/JPNM/TF94_95/Nov1/WriteUpNov1.html

Normal BiodistributionNormal Biodistribution

•4 Hr delayed images show vascular, renal excretion, and liver/spleen uptake•24 Hr delayed images show some bone uptake with significant liver/spleen uptake

Octreoscan Case 1Octreoscan Case 1 69 year old male 69 year old male

presented, history of a presented, history of a 5 cm left hilar lung 5 cm left hilar lung mass found to be small mass found to be small cell lung carcinoma.cell lung carcinoma.

Scan demonstrates two Scan demonstrates two foci of increased uptake foci of increased uptake in the left hilum. in the left hilum.

The patient was started The patient was started on a course of on a course of radiotherapy to the left radiotherapy to the left hilum. hilum.

Octreoscan Case 2Octreoscan Case 2

Intense increased Intense increased tracer localization in tracer localization in the pancreatic mass the pancreatic mass (arrow head) and (arrow head) and multiple abnormal multiple abnormal foci of uptake foci of uptake throughout the liver throughout the liver (arrow) consistent (arrow) consistent with diffuse liver with diffuse liver metastases. metastases.

VIPoma – Endocrine TumorVIPoma – Endocrine Tumor

•Exam of abnormal distribution caused by neuroendocrine tumor red arrows indicate disease•R image is the initial scan with a follow-up still showing significant disease

Peptides - OctreotidePeptides - Octreotide

Patient preparationPatient preparation– Well hydrated - Caution in patients with Well hydrated - Caution in patients with

impaired renal functionimpaired renal function– Bowel preparation - Caution in patients with Bowel preparation - Caution in patients with

insulinomainsulinoma– If patient is taking somatostatin therapeutically, If patient is taking somatostatin therapeutically,

discontinue if possiblediscontinue if possible

Peptides - OctreotidePeptides - Octreotide

InterpretationInterpretation– Focal areas of increased activity outside these Focal areas of increased activity outside these

regions may indicate presence of tumorregions may indicate presence of tumor– PitfallsPitfalls

Bleomycin or external radiation of the lung may Bleomycin or external radiation of the lung may cause local pulmonary accumulation of the cause local pulmonary accumulation of the radiopharmaceutical, particularly along the pleuraradiopharmaceutical, particularly along the pleura

Sites of a recent operationSites of a recent operation

Peptides - OctreotidePeptides - Octreotide

– Pitfalls (continued)Pitfalls (continued) Patients with viral infections of the upper respiratory Patients with viral infections of the upper respiratory

tract may have transient accumulation in the nasal tract may have transient accumulation in the nasal region and the lung hiliregion and the lung hili

Peptides - OctreotidePeptides - Octreotide

Radiation DosimetryRadiation Dosimetry– Critical organCritical organ

SpleenSpleen– 7.39 rads/3 mCi7.39 rads/3 mCi– 14.77 rads/6 mCi14.77 rads/6 mCi

– Effective dose equivalentEffective dose equivalent 1.3 rem/3 mCi1.3 rem/3 mCi 2.61 rem/6 mCi 2.61 rem/6 mCi

Additional Case StudiesAdditional Case Studies