Diagnostic performance of Cu64-dotatate-PET/CT or Ga68-dotatate-PET/CT with 18F-fluorodeoxyglucose (FDG)-PET/CT for neuroendocrine tumor evaluation.
Authors: Covington Matthew F. , Soares Heloisa P. , Kadrmas Dan J. , Butterfield Regan I. , Archibald Zane G. , Stolk Sophie , Mitchell Samuel E. , Puri Sonam , Orgain Nicole G. , Yap Jeffrey T. 
Published: July 2024

e16285

Background: Neuroendocrine tumors (NETs) may be imaged for theranostics with somatostatin receptor (SSTR)-PET/CT like Cu64- or Ga68-dotatate-PET/CT. NETs may also be imaged with 18F-Fluorodeoxyglucose (FDG)-PET/CT based on disease state and insurance coverage. FDG+ and SSTR- disease predicts poor response to Lu177-dotatate therapy, making both scans of possible value. The diagnostic performance of performing both PET/CT studies in close temporal proximity in NET patients is assessed. Methods: This NIH-funded and IRB-approved imaging trial provided FDG- and SSTR-PET/CT in NET patients with RECIST 1.1 measurable disease. A board-certified nuclear radiologist documented detection of the primary NET (if not resected), local, and distant metastatic disease. Each PET/CT pair was assessed for FDG- and SSTR-PET/CT discordant lesions, with location of discordant uptake tabulated. Results: 30 individuals completed FDG-PET/CT and SSTR-PET/CT with either Cu64-dotatate (n = 15) or Ga68-dotatate (n = 15). Studies were performed within 2.4 days average (range 1-10 days). Primary NET site was bowel (n = 15), pancreas (n = 7), lung (n = 7) and unknown (n = 1), with tumor grade 1 (n = 11), grade 1-2 (n = 1), grade 2 (n = 17) and grade 3 (n = 1). Primary NET was detected on FDG-PET/CT in 7/12 cases (58.3%) and on SSTR-PET/CT in 12/12 cases (100%), significantly higher ( p= 0.017). Primary NET was surgically resected in the remaining 18 cases. Local metastases were detected on FDG-PET/CT in 12/30 cases (40%) and on SSTR-PET/CT in 19/30 cases (63.3%), significantly higher ( p= 0.006). Distant metastases were detected on FDG-PET/CT in 19/30 cases (63.3%) and on SSTR-PET/CT in 24/30 cases (80%), trending significantly higher ( p= 0.057). Discordant detection (yes/no for any disease) of primary, local, and/or distant disease was seen in 13/30 cases (43.3%). An equal number of lesions were detected between FDG- and SSTR-PET/CT in 4/30 cases (13.3%), more lesions on FDG-PET/CT in 1/30 (3.4%), and more lesions on SSTR-PET/CT in 25/30 (83.3%). For SSTR-PET/CT, more lesions were detected in the liver (n = 16), lymph nodes (n = 15), bone (n = 6) and bowel (n = 5) than on paired FDG-PET/CT. Disease was exclusively detected on SSTR-PET/CT in 5/30 (16.7%), and in no case on FDG-PET/CT. FDG-PET/CT showed 2/30 (6.7%) cases with exclusively FDG+ liver disease, both in patients with primary lung NETs (2/7, 28.9%). Conclusions: SSTR-PET/CT showed superior detection of primary and locoregional disease, and detected more distant disease sites than FDG-PET/CT. Discordant uptake between PET/CT studies was identified in nearly half of cases, with highest discordance noted in liver and lymph nodes. Discordant FDG+ and SSTR- disease was only seen in patients with primary lung NET, which is a negative prognostic factor for Lu177-dotatate therapy, and may justify the need for having both scans in this group.