Paediatric insulinomas often appear dark on FDOPA PET scans, not bright

Insulinomas are among the rarest tumours in medicine, and in children they are rarer still. When four children treated at a single specialist centre over sixteen years all underwent the same specialised scan, the results defied what the imaging textbooks would predict. In three of the four cases, the tumour showed up not as a bright hotspot of radioactive tracer, as expected, but as a dark void, a phenomenon known as photopenia, against the background of the pancreas. The finding, reported in a short communication in EJNMMI Reports, suggests that paediatric insulinomas may behave differently on [18F]-dihydroxyphenylalanine ([18F]FDOPA) positron emission tomography-computed tomography (PET-CT) than their adult counterparts, and that recognising this atypical pattern could matter for children whose cure depends on finding the tumour before surgery.

The team, led by Sameera Hannah Auckburally of Royal Manchester Children’s Hospital, together with colleagues including Ross J. Craigie, Konrad Mohnike, Sabrina Alam, Sarah Worthington, Indraneel Banerjee and Rakesh Sajjan, retrospectively reviewed the medical notes and investigations of children with histologically proven insulinoma who presented to the hospital between 2008 and 2024. Four cases were identified. All of the children had undergone an [18F]FDOPA PET-CT scan as part of their diagnostic workup, three of the scans being performed at Royal Manchester Children’s Hospital in the United Kingdom and one at Sana Klinikum in Berlin, Germany.

Insulinomas are rare pancreatic neuroendocrine tumours that arise from the insulin-producing beta cells of the pancreatic islets. Their reported incidence is 1 to 4 per million people per year, and paediatric cases account for only about 1 percent of all insulinomas, which is why the literature on children is so sparse. The tumours typically announce themselves through recurrent episodes of hypoglycaemia, which can produce neuroglycopenic symptoms such as confusion, drowsiness, seizures, syncope and behavioural difficulties. Because these symptoms are non-specific and because insulinoma is far less common in children than congenital hyperinsulinism, diagnosis can be difficult. Ninety percent of insulinomas are benign, malignancy may occur in 5 to 10 percent, and the majority are solitary lesions, although approximately 10 percent present as multiple lesions either concurrently or sequentially over time.

Diagnosis of suspected cases rests on detecting insulin at the time of hypoglycaemia, in the same way as in children with congenital hyperinsulinism. An undetectable insulin level does not always exclude an insulinoma, and because insulinoma cells produce relatively more proinsulin than normal pancreatic beta cells, proinsulin assays are sometimes used as a diagnostic adjunct. Once an insulinoma is suspected biochemically, preoperative localisation of the tumour with radiological and isotope imaging is common practice, because successful surgical resection can cure the condition. Multiple non-invasive modalities are available, including ultrasound, computed tomography, magnetic resonance imaging and somatostatin receptor scintigraphy, but these generally localise only 10 to 60 percent of primary pancreatic neuroendocrine tumours. Endoscopic ultrasound is considered the most sensitive modality for imaging small pancreatic neuroendocrine tumours.

The logic behind using [18F]FDOPA as a tracer comes from tumour biology. Neuroendocrine tumours have been found to have increased activity of the enzyme L-DOPA decarboxylase, which allows [18F]FDOPA to be used to image insulinomas in PET-CT scans. Insulinomas are generally considered to be [18F]FDOPA avid, with greater uptake and retention in tumour cells than in surrounding tissue. It is also generally known that there is increased uptake of [18F]FDOPA in focal lesions in infants with congenital hyperinsulinism, and in adult insulinomas uptake is generally increased for the same enzymatic reason. Against this expectation, the Manchester team report unusual photopenia at the tumour site in three of their four paediatric patients.

The first case was a ten-year-old boy who presented to his local hospital with acute confusion associated with hypoglycaemia. He was started on diazoxide and magnetic resonance imaging revealed a tumour in the pancreatic tail, and further testing showed a mutation in MEN1. On transfer to the specialist centre, he underwent [18F]FDOPA PET-CT with sequential images obtained up to 90 minutes after injection of 4 MBq/kg of the tracer, alongside a diagnostic contrast CT for image fusion. An area of photopenia was observed in the tip of the tail of the pancreas, corresponding to a lesion measuring 13 by 10 millimetres identified on MR imaging, while the rest of the pancreas showed diffuse physiological uptake. Because of the potential for multifocal disease in insulinomas related to multiple endocrine neoplasia, he underwent endoscopic ultrasound, which demonstrated an 11-millimetre-wide lesion. The tumour was resected laparoscopically, curing his hypoglycaemia, and histology showed a well-differentiated insulin-producing neoplasm of the pancreas, Grade 1, pT2.

The second case was a 14-year-old girl who presented with a hypoglycaemic seizure after a three-month history of short-lived episodes of confusion and unusual speech patterns. A controlled fast revealed hypoglycaemia after 17 hours with inappropriately raised insulin and C-peptide levels, and gene panel testing for congenital hyperinsulinism and MEN1 was negative. MR imaging demonstrated a 12 by 9 millimetre lesion in the neck of the pancreas which restricted diffusion but was occult on post-contrast sequences. The [18F]FDOPA PET-CT showed no focal increased tracer uptake on either early or delayed phase imaging, but there was an area of photopenia at the site of the known lesion, with physiological tracer distribution elsewhere in the pancreas. She underwent ultrasound-guided surgical resection by distal pancreatectomy at laparotomy, histopathology confirmed a Grade 1, pT1 insulinoma, and following resection she was cured of hypoglycaemia with no recurrence at annual review.

The third case was a six-year-old boy who presented with atypical seizures, initially not recognised as being related to hypoglycaemia, and who had been taking lamotrigine for a year and a half before a hypoglycaemic seizure prompted a hypoglycaemia screen that confirmed biochemical evidence of excess insulin secretion. An MR scan suggested a pancreatic lesion in the uncinate process, best demonstrated on T2-weighted sequences and relatively hypo-intense on T1, measuring 1.4 by 1 centimetre in the axial plane. An [18F]FDOPA scan performed in Germany confirmed a well-defined lesion within the pancreas with reduction of isotope uptake. He underwent partial pancreatectomy complicated by significant post-operative haemorrhage secondary to pancreatic leak, which required a jejuno-pancreatic Roux-en-Y procedure. Pancreatic histology confirmed an insulinoma, and in the post-operative period he was found to carry a mutation in MEN1.

The fourth case stood apart. A four-year-old girl presented with symptoms of hypoglycaemia, and on further questioning it appeared that brief symptoms of drowsiness and fatigue had been occurring for at least a year. A hypoglycaemia screen showed biochemical evidence of hyperinsulinism, and she was started on diazoxide with partial response. In contrast to the other three patients, this child had avid isotope uptake on [18F]FDOPA PET-CT, with intense increased uptake in the uncinate process demonstrated on maximum intensity projection and axial PET and fused images, and an enhancing lesion on contrast CT. A histologically confirmed insulinoma was removed from the uncinate process of the pancreas with subsequent cure from hypoglycaemia, and gene panel investigations for congenital hyperinsulinism and MEN1 testing were negative.

In their discussion, the authors note that in three of the four cases the lesions demonstrated relative photopenia, with reduced tracer uptake compared to surrounding pancreatic tissue, rather than the expected focal avidity, and that only one patient showed increased tracer uptake, aligning with typical adult imaging patterns. The reasoning behind this variable tracer avidity is unclear, and the authors emphasise that because the lesions were still distinct against the rest of the pancreas, the scans remained essential for surgical planning, with all four cases undergoing successful tumour resection. They acknowledge the limitations of the series: the small sample size and the retrospective nature of data collection. Nonetheless, they argue that photopenia on [18F]FDOPA PET-CT may be a more frequent finding than increased uptake in paediatric insulinomas, that recognising this atypical pattern is important for accurate tumour localisation before surgical management, and that further studies are needed to validate the findings and to find a mechanistic explanation for why these rare childhood tumours can appear dark rather than bright on a scan designed to light them up.

Subject of Research: A retrospective case series of four children with insulinoma describing unusual photopenia on [18F]FDOPA PET-CT imaging.

Article Title: Unusual [18F]FDOPA PET-CT maging of insulinomas in children

Article References: Auckburally, S. H., Craigie, R. J., Mohnike, K., Alam, S., Worthington, S., Banerjee, I., & Sajjan, R. (2026). Unusual [18F]FDOPA PET-CT maging of insulinomas in children. EJNMMI Reports, 10(1), Article 55. https://doi.org/10.1186/s41824-026-00331-6

Image Credits: AI Generated

DOI: 10.1186/s41824-026-00331-6

Keywords: insulinoma, paediatric, [18F]FDOPA, PET-CT, photopenia, pancreatic neuroendocrine tumour, hypoglycaemia, tumour localisation, case series, Royal Manchester Children's Hospital, congenital hyperinsulinism, surgical resection