Somatostatin Receptor Imaging

Somatostatin receptor imaging shows tumours that carry somatostatin receptors on their surface, mainly neuroendocrine tumours. A radiolabelled somatostatin analogue is injected intravenously, binds to the receptors and is retained in tumour tissue. The result maps the primary tumour and its metastases, and shows whether peptide receptor radionuclide treatment is possible.

Positron emission tomography with gallium-68 DOTATATE, DOTATOC or DOTANOC is now the preferred method.

The usual dose is 100 to 200 MBq (about 2 MBq for each kg) intravenously, with imaging 45 to 90 minutes later from the skull base to the mid-thigh, and a low dose CT for localisation and attenuation correction. Copper-64 DOTATATE gives a longer imaging window.

Indium-111 pentetreotide SPECT with images at 4 and 24 hours is an older method with lower sensitivity.

The effective dose is about 3 to 5 mSv for gallium-68 agents. Neuroendocrine tumours have an incidence of about 5 to 7 in 100 000 each year and are often found late, with liver metastases in 30 to 40% at diagnosis.

Receptor PET detects well differentiated tumours with a sensitivity of 90 to 95% and a specificity of 90 to 95%, higher than CT, MRI and the older SPECT method, and it changes management in about a third of patients.

Indications.

• Staging of neuroendocrine tumours of the small bowel, pancreas, lung (carcinoid), stomach, rectum and other sites.
• Search for the primary tumour in a patient with neuroendocrine liver metastases or a carcinoid syndrome.
• Restaging after surgery or treatment, and detection of recurrence when tumour markers rise.
• Selection for peptide receptor radionuclide treatment (uptake higher than normal liver) and for somatostatin analogue treatment.
• Phaeochromocytoma and paraganglioma, particularly in hereditary syndromes and metastatic disease.
• Medullary thyroid cancer with raised calcitonin and negative imaging.
• Tumours that cause osteomalacia (mesenchymal tumours with phosphate wasting).
• Meningioma (extent and planning of radiotherapy), and small cell lung cancer in selected cases.
• Hormone secreting syndromes with an unknown source, for example insulinoma (variable receptor expression), gastrinoma and VIPoma.
• Sarcoidosis and other inflammatory disease, as an incidental use.

Contraindications and precautions.

• Pregnancy: avoid unless essential. Breast feeding: interrupt feeding for a few hours (the local rule decides), and avoid close contact with infants for several hours.
• Somatostatin analogue treatment lowers tumour uptake. Short acting octreotide is stopped for 24 hours before the scan, and long acting depot preparations are timed so that the scan is done just before the next dose (usually 3 to 4 weeks after the last injection) if the treatment cannot be stopped.
• Hydration and frequent voiding reduce the bladder dose.
• Allergy to the peptide is rare.
• Renal impairment does not change the procedure, but kidney uptake is higher with poor function.
• The patient should lie still for 20 to 30 minutes for PET images.
• Recent peptide receptor radionuclide treatment or large injections of contrast do not preclude the study.

Preparation and technique.

No fasting is needed. The patient drinks plenty of water and empties the bladder before imaging. The tracer is injected intravenously, and the patient rests for 45 to 90 minutes before the scan.

A low dose CT is taken for localisation and attenuation correction. The PET acquisition covers from the skull base to the thighs, and extends to the whole body when needed. Diagnostic CT or MRI with contrast is added for the liver and for surgical planning.

Images are read with attention to uptake in comparison with normal liver and spleen. Uptake values (SUV) are measured, and the number, site and size of lesions are listed.

Normal appearances.

Physiological uptake is high in the spleen, kidneys and adrenal glands, moderate in the liver, pituitary and thyroid, and variable in the salivary glands and the uncinate process of the pancreas. The bowel and bladder show tracer excretion. Bones, muscle and lung show little uptake.

Interpretation.

• Neuroendocrine tumour: focal uptake higher than the background liver, usually much higher than the liver in well differentiated tumours. Primary tumours are found in the small bowel mesentery, pancreas, lung and stomach.
• Metastases: liver, nodes, bone and peritoneum. Bone and nodal disease are detected earlier than with CT. Small liver lesions are shown better with MRI.
• Receptor positive tumours (uptake higher than the liver in all or most lesions) can be treated with somatostatin analogues and peptide receptor radionuclide therapy.
• Phaeochromocytoma and paraganglioma: avid uptake in adrenal and extra-adrenal sites, including head and neck paragangliomas.
• Poorly differentiated tumours (high grade) may be receptor negative, and then fluorodeoxyglucose PET is more informative. A mismatch of receptor negative and glucose avid lesions marks aggressive disease.
• Mesenchymal tumours causing osteomalacia: a small focal uptake in bone or soft tissue.
• Meningioma: intense uptake that separates tumour from normal dura and bone.
• Inflammation: uptake in granulomas, thyroid disease, arthritis and healing fractures is a source of false positives.
• Response to treatment is judged from uptake and size, together with tumour markers (chromogranin A, 5-HIAA, hormone levels).
• Selection for treatment: all measurable lesions should have uptake greater than the liver.

Critical values and findings needing immediate action.

• Large tumour mass causing bowel obstruction, bleeding or ischaemia: urgent surgical review.
• Spinal or skull base lesion with neurological signs: urgent MRI and specialist review.
• Widespread liver disease with carcinoid syndrome or hormone crisis: octreotide and critical care input.
• Cardiac involvement from carcinoid disease (right heart valve lesions): echocardiography and cardiology review.
• Phaeochromocytoma suspected on the scan: do not biopsy, start alpha blockade before any procedure.

Limitations and artefacts.

• Poorly differentiated and some small tumours do not express receptors, and are missed.
• Physiological uptake in the uncinate process and head of the pancreas mimics a tumour. Delayed images or CT help.
• Inflammatory and benign lesions (meningioma, thyroid disease, osteophytes, healing fractures, accessory spleen) can take up tracer. A splenule after splenectomy is a common error.
• Somatostatin analogues lower uptake, and timing relative to the drug is important.
• Small liver metastases may be missed or hidden by the high background in a liver with extensive disease.
• Bladder and kidney activity hide pelvic and renal lesions.
• Insulinomas often have few receptors, and a negative scan does not exclude them.
• The test does not give tumour grade. Histology, Ki-67 index and fluorodeoxyglucose PET are needed.
• Gallium-68 generators limit supply and availability.

Special groups.

• Children: rare use, mainly for neuroblastoma and paraganglioma, with a weight based dose.
• Patients with hereditary syndromes (multiple endocrine neoplasia, von Hippel-Lindau disease, hereditary paraganglioma): used for surveillance.
• Patients on long acting analogues: schedule at the end of the dosing interval.
• Patients with renal failure: higher background and risk of treatment toxicity.
• Pregnant patients: avoid.
• Regions: neuroendocrine tumours are under diagnosed. Receptor PET is available in few centres, so CT, MRI, ultrasound, endoscopy and biochemical tests (chromogranin A, urinary 5-HIAA) are used.

Follow up tests.

• Contrast CT or MRI of the liver and abdomen.
• Fluorodeoxyglucose PET-CT for high grade or discordant disease.
• Endoscopic ultrasound and biopsy with grading (Ki-67).
• Chromogranin A, urinary 5-hydroxyindoleacetic acid, gastrin, insulin, calcitonin, plasma metanephrines.
• Echocardiography in carcinoid syndrome.
• Genetic testing in hereditary syndromes.
• Referral to oncology, endocrinology, surgery or nuclear medicine for treatment.