Use of full-dose contrast-enhanced CT for extrahepatic staging using Gallium-68-DOTATATE PET/CT in patients with neuroendocrine tumors

PURPOSEStudies have demonstrated that positron emission tomography/computed tomography (PET/CT) with Gallium-68 (⁶⁸Ga)-labeled somatostatin analogues are effective at detecting metastatic disease in neuroendocrine tumors (NET), especially extrahepatic metastases. However, PET in combination with full-dose contrast-enhanced CT (ceCT) exposes patients to higher radiation (~25 mSv). The use of non-contrast-enhanced low-dose CT (ldCT) can reduce radiation to about 10 mSv and may avoid contrast-induced side effects. This study seeks to determine whether ceCT could be omitted from NET assessments.METHODSWe retrospectively compared the performance of PET/ldCT versus PET/ceCT in 54 patients (26 male, 28 female) who had undergone a ⁶⁸Ga-DOTATATE PET/CT. The selection criteria were as follows: available ldCT and ceCT, histologically confirmed NET, and follow-up of at least 6 months (median, 12.6 months; range, 6.1–23.2 months). The PET/ldCT and PET/ceCT images were analyzed separately. We reviewed metastases in the lungs, bones, and lymph nodes. The results were compared with the reference standard (clinical follow-up data).RESULTSThe PET/ceCT scans detected 139 true-positive bone lesions compared with 140 lesions detected by the PET/ldCT scans, 106 true-positive lymph node metastases (PET/ceCT) compared with 90 metastases detected by the PET/ldCT scans, and 26 true-positive lung lesions (PET/ceCT) compared with 6 lesions detected by the PET/ldCT scans. The overall lesion-based sensitivity for full-dose PET/ceCT was 97%, specificity 86%, negative predictive value (NPV) 93%, and positive predictive value (PPV) 93%. The overall lesion-based sensitivity for PET/ldCT was 85%, specificity 73%, NPV 72%, and PPV 85%.CONCLUSIONThis study presents the first evidence that ceCT should not be omitted from extrahepatic staging using ⁶⁸Ga-DOTATATE PET/CT in patients with NET. ceCT alone can be used as a follow-up to reduce radiation exposure when the patient has already undergone PET/ceCT and suffers from non-DOTATATE-avid NET.

Previous studies have shown the importance of DOTATOC, DOTATATE, and DOTANOC PET/CT imaging in the diagnosis and accurate staging of neuroendocrine tumors (NET) (1–3). The use of radiolabeled somatostatin analogs in PET/CT has become the standard protocol in NET staging. For many years, octreotide-scintigraphy was used for NET detection and assessment, but this practice has recently been replaced by combined, integrated PET/CT imaging with ⁶⁸Ga-labelled somatostatin analogues. The new method yields higher spatial resolution and facilitates tracer uptake quantification, and ⁶⁸Ga PET/CT has increasingly replaced the use of contrast-enhanced computed tomography (ceCT) alone. ⁶⁸Ga PET/CT provides for precise staging and allows the physician to assess the feasibility of peptide receptor radionuclide therapy (4, 5). There is evidence that PET/ceCT can be beneficial for patients with NET and the ENETS guidelines, among others, recommend PET/ceCT for staging NETs (6–8). However, to date, there is no mandatory consensus on the appropriate ⁶⁸Ga PET/CT protocol for assessing NET. A patient can undergo PET with non-contrast-enhanced low-dose CT (ldCT) or with full-dose ceCT. The diagnostic benefit of surplus ceCT has been assessed particularly for the detection and staging of ¹⁸F-fluorodeoxyglucose (FDG)- avid lymphoma (5) and NET abdominal lesions (9). The benefits of ceCT over PET/ldCT in the detection of extrahepatic metastases have not been analyzed with that kind of detail. As the ceCT method results in substantial radiation exposure (up to 25 mSv), depending on the type of CT machine, any potential dose reduction is desirable. While these levels of exposure are within the limits recommended by Huang et al. (10), they surpass those given by Persson et al. (11). In addition, contrast medium can cause adverse reactions such as hyperthyroidism and renal failure, so it should not be administered without cause, although current ESUR guidelines suggest that contrast media’s adverse effects have been widely overestimated (12). This study addresses whether ceCT is necessary for the detection and assessment of NET extrahepatic metastases and if PET/ldCT is sufficiently reliable.