What Is an Insulinoma?
An insulinoma is a rare tumour that develops in the insulin-producing beta cells of the pancreas. These tumours secrete insulin even when blood sugar levels are already low, leading to a condition called hypoglycaemia. Symptoms include episodes of sweating, confusion, dizziness, trembling, and in severe cases, loss of consciousness.
Most insulinomas are small, often less than two centimetres in diameter, and the vast majority are benign. Surgery is the standard treatment and is usually curative. The challenge, however, is finding the tumour in the first place.
Why Conventional Imaging Struggles
CT scans and MRI are the first-line imaging tools for most abdominal conditions. For insulinomas, though, their track record is inconsistent. Studies report detection rates ranging from 30% to 80% depending on the size and location of the tumour. A lesion that is only 8 or 10 millimetres across, sitting within the pancreatic tissue, can be remarkably difficult to spot on cross-sectional imaging.
Endoscopic ultrasound (EUS) improves detection by placing the imaging probe close to the pancreas via the stomach or duodenum. It picks up many tumours that CT and MRI miss, but it is operator-dependent and invasive. Some insulinomas still elude detection even after multiple rounds of imaging, leaving patients and their surgical teams without a clear target.
This is where nuclear medicine imaging with an exendin PET scan offers a different approach.
How Exendin PET Targets GLP-1 Receptors
Insulinomas express high levels of a receptor called GLP-1R (glucagon-like peptide-1 receptor) on their cell surface. This receptor is part of the normal hormonal signalling system in the pancreas, but insulinoma cells carry far more of it than surrounding healthy tissue.
Exendin-4 is a synthetic peptide that binds to the GLP-1 receptor with high affinity. When labelled with a radioactive isotope, typically Ga-68, it becomes a PET tracer that homes in specifically on cells expressing GLP-1R. After injection, the tracer circulates through the body and accumulates in the insulinoma, producing a bright signal on PET imaging.
Because the tracer targets a receptor rather than general metabolic activity, it can detect tumours that are too small or too metabolically similar to normal pancreatic tissue for FDG PET or CT to identify.
The Scan Procedure
Patients undergoing an exendin PET scan can expect the following steps:
Preparation: No prolonged fasting is typically required, though your nuclear medicine team will provide specific instructions. Medications that affect blood sugar may need adjustment beforehand. Discuss this with your referring physician.
Tracer injection: A small dose of Ga-68 labelled exendin-4 is injected intravenously. The injection itself takes a few seconds and feels similar to a routine blood draw.
Uptake period: After injection, there is a waiting period to allow the tracer to bind to GLP-1 receptors. This usually takes about 40 to 60 minutes.
Image acquisition: The patient lies on the PET CT scanner bed while whole-body images are acquired. The PET component captures the radioactive signal from the tracer, and the CT provides anatomical context. Combined, these images pinpoint the location of any GLP-1R-expressing tissue.
Duration: From arrival to completion, the appointment takes roughly two hours. The scan itself lasts about 20 to 30 minutes.
One point patients should be aware of: the exendin tracer can sometimes cause mild nausea, as GLP-1 receptor activation in the gut can trigger that sensation. This is usually brief and resolves without treatment.
Clinical Evidence and Detection Rates
Published studies have shown that exendin PET can detect insulinomas with sensitivity rates above 90% in many patient cohorts. In head-to-head comparisons with CT and MRI, exendin PET has found tumours that were invisible on conventional imaging. It has also correctly identified the location of the tumour within the pancreas (head, body, or tail), which is critical information for the surgical team planning the operation.
In a subset of patients with what is called occult insulinoma, where the diagnosis is certain based on blood tests but no imaging modality has been able to locate the tumour, exendin PET has changed management by finally revealing where the lesion sits.
When Is Exendin PET Recommended?
This scan is not a first-line investigation for everyone with low blood sugar. It is typically considered in the following situations:
- Biochemically confirmed insulinoma where CT, MRI, and endoscopic ultrasound have failed to locate the tumour
- Pre-surgical planning when the exact position within the pancreas needs to be confirmed
- Suspected recurrent insulinoma after previous surgery
- Evaluation of patients with MEN-1 syndrome (multiple endocrine neoplasia type 1), who can develop multiple pancreatic neuroendocrine tumours including insulinomas
- Distinguishing insulinoma from nesidioblastosis, a diffuse condition of abnormal beta cell function that requires different treatment
In each case, the decision to proceed with exendin PET should come from the treating endocrinologist or surgeon in consultation with the nuclear medicine team. The scan adds value when there is a genuine clinical gap that conventional imaging has not filled.
What Happens After the Scan?
If the exendin PET scan identifies the insulinoma, the surgical team uses that information along with any other available imaging to plan the operation. Depending on the size and location, surgery may involve removing just the tumour (enucleation) or a portion of the pancreas (partial pancreatectomy). Success rates for surgery are high when the tumour has been accurately localised beforehand.
If the scan does not show a clear lesion, the endocrinologist may recommend additional investigations or a period of observation with medical management of blood sugar levels. A negative scan does not rule out the diagnosis entirely, as very small or atypical tumours may still be difficult to detect.
A Targeted Solution for a Difficult Problem
Insulinomas are rare, and locating them has historically been one of the more frustrating challenges in endocrine surgery. The exendin PET scan addresses that challenge by targeting the specific molecular signature of these tumours. For patients living with repeated hypoglycaemic episodes and no clear answer on conventional imaging, this scan can provide the clarity needed to move toward definitive treatment.
If you have been diagnosed with or are being evaluated for an insulinoma, discuss the role of exendin PET imaging with your endocrinologist or nuclear medicine physician.