Prospective Evaluation of 68Ga-DOTATATE and 18F-DOPA PET Scans in Detecting Tumors Causing Ectopic ACTH Syndrome.

Context: Identification of tumors causing ectopic ACTH syndrome (EAS) is challenging. 68Ga-DOTATATE (DOTA) and 18F-DOPA (DOPA) positron emission tomography/computed tomography (PET/CT) scans are promising imaging modalities warranting further evaluation.

Objective: This work aimed to compare DOTA and DOPA PET/CT performance in detecting ectopic sources of adrenocorticotropin (ACTH).

Methods: A prospective comparison of DOTA, DOPA, and conventional imaging modalities in EAS was conducted at a tertiary referral center. Participants included 24 patients with EAS from neuroendocrine tumors confirmed by pathology and/or biochemical cure. Interventions included DOTA PET/CT, DOPA PET/CT, CT, MRI, gated cardiac CT/MRI, and Octreoscan (OCT) performed between 2014 and 2024. Main outcome measures included sensitivity (Se) and positive predictive value (PPV) for each imaging modality, and 7 combinations thereof, in patients with identified tumors.

Results: Of functional scans, Se for DOPA was higher than OCT (Se 88%; 95% CI, 67%-97% vs 31%; 95% CI, 10%-61%) and overlapped DOTA (Se 79%; 95% CI, 57%-92%). Among structural modalities, CT had the highest Se (96%; 95% CI, 76%-100%) when interpreted knowing results of functional scans; Se was 57% (95% CI, 35%-76%) without those data. Cardiac CT/MRI had the highest PPV (100% for each). Combinations of CT/MRI plus DOTA and/or DOPA provided high PPVs (89%-100%) with Se 64% to 87%; all CIs overlapped. Combined CT and MRI without functional scans provided PPV 79% with Se 55%, although CI overlapped with combinations that included DOTA/DOPA.

Conclusion: DOTA and DOPA improve tumor detection in EAS by increasing Se of structural scans and PPV of detected lesions. The two scans are complementary and should be integral to imaging strategies for EAS. However, DOPA is not currently approved by the Food and Drug Administration for this indication.