18F-DOPA PET and enhanced CT imaging for congenital hyperinsulinism

Abstract

Congenital hyperinsulinism (CHI) is the most common cause of persistent hypoglycaemia in infants and children. Histologically, there are two subgroups, diffuse and focal. The aim of this study was to evaluate the accuracy of (18)F-fluoro-L-dihydroxyphenylalanine ((18)F-DOPA) PET/computed tomography (CT) and contrast-enhanced CT in distinguishing between focal and diffuse lesions in infants with CHI who are unresponsive to medical therapy. In addition, this paper describes the detailed protocol used for imaging and analysis of (18)F-DOPA PET/CT images in our clinical practice. Twenty-two (18)F-DOPA PET/CT and contrast-enhanced CT imaging studies were carried out on 18 consecutive patients (nine boys and nine girls) with CHI (median age, 2 years and 1 month; range, 1-84 months) who had positive dominant ABCC8 mutation genetic results or negative ABCC8/t results but did not respond to first-line medical therapy with high-dose diazoxide. (18)F-DOPA was produced by the cyclotron unit of Woolfson Molecular Imaging Centre, Manchester, and transported to our centre in central London after synthesis and implementation of quality control measures. (18)F-DOPA was administered intravenously at a dose of 4 MBq/kg, and iodine contrast medium was injected intravenously at a dose of 1.5 ml/kg. Single bed position PET/CT images of the pancreas were acquired under light sedation with oral chloral hydrate. Four PET dynamic data acquisition scans were taken 20, 40, 50 and 60 min after injection for a duration of 10 min each. The results were assessed by visual interpretation and quantitative measurements of standardized uptake values (SUVs) in the head, body, and tail of the pancreas. Of the 18 patients, 13 showed diffuse and five showed focal (18)F-DOPA PET pancreatic uptake. Three regions of interest were drawn over the head, body and tail of the pancreas to calculate the SUV(max). Using the formula - highest SUV(max)/next highest SUV(max) - a ratio was calculated. Five patients had an accumulation of F-DOPA in the pancreas and an SUV ratio greater than 1.5, indicating focal disease with an SUV(max) more than 50% higher than that of the unaffected areas of the pancreas. The remaining 13 patients had diffuse accumulation of (18)F-DOPA in the pancreas (SUV ratio<1.3). Using this ratio, a focal lesion can be distinguished from diffuse uptake and normal pancreatic uptake. The sizes of these regions of interest varied according to the age of the child. All patients diagnosed with focal lesions underwent surgery and were cured eventually. Lesions were accurately localized by PET/CT and confirmed by histological results after surgery. Three of these patients had to undergo second (18)F-DOPA scans and second surgeries after unsuccessful excision during their first surgery. Three patients with diffuse disease underwent a partial pancreatectomy, and histological results confirmed diffuse disease. One patient was cured and two remain on high-dose diazoxide therapy because of persistent hypoglycaemia. (18)F-DOPA PET/CT offers excellent differentiation of focal from diffuse CHI, and the contrast-enhanced CT technique permits precise preoperative localization of the lesion and anatomical landmarks.