Combined [¹⁸F]Fluorodeoxyglucose PET and [¹²³I]Iodometomidate-SPECT for diagnostic evaluation of indeterminate adrenal neoplasias-the cross-sectional diagnostic test accuracy study FAMIAN.

Abstract

Adrenal tumours are frequently detected by conventional imaging. However, computed tomography and magnet resonance imaging have limited specificity in classifying the most prevalent tumour type, adrenocortical adenoma (ACA), which typically does not require surgery. We proposed that combined molecular imaging with [¹⁸F]Fluorodeoxyglucose-positron emission tomography (FDG PET) and [^123I]Iodometomidate-single photon emission tomography (IMTO SPECT) improves non-invasive classification of ACA. This cross-sectional, multicentre diagnostic study included patients (≥30 years) with non-functioning indeterminate adrenal masses (>3 cm or increase >1 cm, Hounsfield units [HU] ≥10 on unenhanced computed tomography [CT]) scheduled for surgery. Using histopathology as the reference, we assessed the accuracy of FDG/IMTO imaging as an ACA-test, assuming that low FDG with high IMTO uptake is indicative of ACA, with a focus on high specificity and moderate to high sensitivity. We also investigated its accuracy in detecting or excluding adrenocortical carcinoma (ACC) and evaluated FDG and unenhanced CT in assessing malignancy. EudraCT 2012-003604-13; ClinicalTrials.gov-identifier NCT02010957. From July 2015 to December 2020, 85 patients were enrolled, with 77 included in the final analysis (53 benign, 30 ACA, 9 ACC). FDG/IMTO-imaging classified ACA with high specificity (95·7% [95% CI 85·2%-99·47%]), high positive predictive value (87·5% [95% CI 61·7%-98·4%]) and high positive likelihood ratio (11·1 [95% CI 3·2-122]). However, sensitivity was low (48·3% [95% CI 29·4%-67·5%]) due to moderate/high FDG uptake in 14 of 30 ACA. Malignant masses were classified with high sensitivity but low-to-moderate specificity by both unenhanced CT (cut-off HU ≥20 sensitivity 100% [95% CI 85·8%-100%], specificity 26·4% [95% CI 15·3%-40·3%]) and FDG (visual analysis sensitivity 95·8% [95% CI 78·9%-99·9%], specificity 62·3% [95% CI 47·9%-75·2%]). All four study-related AEs were grade 1, the seven serious AEs were not study-related. Combined FDG/IMTO-imaging classifies ACA with high specificity, potentially reducing unnecessary surgery. A sub-group of FDG-positive ACA lowers sensitivity. German Research Foundation and EU-FP7.