Introduction
- Insulinoma is a rare neuroendocrine tumor arising from pancreatic beta cells with an incidence of 0.4 per 1,00,000 people per year. It is the most common cause of endogenous hyperinsulinemic hypoglycemia in adult patients with out diabetes.
Clinical Features:
- Fasting Hypoglycemia
- Neuroglycopenia
- Post prandial hypogylcemia
Investigations:
Biochemical Parameters:
There is high serum insulin concentration.
CECT:
Contrast enhancing tumors in the portal venous inflow phase and in the pancreatic contrast enhancment phase.
EUS:
Sensitivity is 80-90%. But limited to tumors localised in head and body of pnacreas.
Role of Nuclear Medicine
Somatostatin receptor imaging is considered the most sensitive method for detecting Neuroendocrine tumors due to marked overexpressing somatostatin receptors. However, somastatin receptors are insufficiently expressed in many insulinomas. SSTR sensitivity is 20 - 60%.
GLP-1 Receptor:
- Glucagon like peptide -1 receptor is highly overexpressed on benign insulinoma cells surface with very high incidence and extreme high density.
- No other peptide receptor has been found to exhibit such high expression levels in insulinoma.
- Physiologically the GLP-1 receptior is expressed in pancreas, duodenum, neurohypophydid, intestines, breasr, thyroid gland, kidney and lung.
- Most tissue express GLP-1 receptor at a low level, whereas the most striking receptor expression is found in the neurohypophysis.
- In pancreas, both islets and acini express GLP-1 receptors, with much higher receptor level in the islets.
- In tumors, the highest density of GLP-1 receptor expression was found in insulinoma, and virtually all benign insulinomas highly overexpress GLP-1 receptors with an approximately five fold higher density over normal Beta cells.
- GLP-1 receptors are also expressed in various endocrine tumors, such as pheochromocytoma, gastrinoma as well as in brain tumors, embryonic tumors at a low density whereas GLP-1 receptors are vitually absent in carcinoma and lymphomas.
Exendin -4
It is an analogue of GLP-1. GLP-1 receptor mediates the action of GLP-1, released from the entero-endocrine L cels in the small intestines in response to food intake.
- GLP-1 is the most important glucose dependent insulin secetagogues.
- It stimulates glucose dependent insulin synthesis and secretion, promotes Beta cells proliferation and inhibits apoptosis.
- It also controls glycemia- via inhibition of gastric emptying, food intake, glucagon excretion from pancreatic alpha cells.
- Native GLP-1 is rapidly degraded by endogenous enzyme - dipeptidyl peptidase IV with a biological half life of 1 to 2 minutes.
- Exendin-4 is a biologically active peptide isolated from venom of the Gila Monster Lizards.
- It has similar binding affinity to GLP-1 receptor.
- It has a specific internalization in beta cell tumor cells after binding with GLP-1 receptors and shows a high metabolic stability in beta cell tumor cells.
- It is resistant to dipeptidyl peptidase IV cleavage and more than 70% of the intact peptide remains in human blood serum after 24hrs.
Imaging in Insulinoma:
First tracer- 125 I GLP amide and 125 I exendin 3- low stability and efficiency. Then - 111 In labelled DTPA exendin 4 - localised occult insulinoma. Then 111 In labelled DOTA exendin 4 - used for localization. Then 99m Tc labelled HYNIC exendin 4- Sensitivity and specificity of 100%.
Due to the small size of insulinoma (usually <2cm), GLP-1 receptor imaging with PET may offer an advanatage over SPECT with higher spatial resolution, sensitivity and imaging contrast in localizing insulinoma.
- Exendin based PET tracers labeled with 68Ga, 18F, 64Cu, 89Zr.
- Generator produced 68Ga is preferred due to availability, low price and short physical half life of 68 minutes, eg. 68Ga NOTA exendin - 4, Sensitivity = 97.7% and PPV= 100%.
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