Asia Oceania Journal of Nuclear Medicine and Biology

Asia Oceania Journal of Nuclear Medicine and Biology

[18F]FMISO PET in metastatic neuroendocrine tumours: a pilot study

Document Type : Original Article

Authors
David L Chan 1
Alice Conner 2
Nick Pavlakis 1
Elizabeth Bailey 3
Alireza Aslani 3
Kathy Willowson 4
Connie Diakos 1
Elizabeth J Bernard 4
Stephen Clarke 1
Alexander Engel 2
Paul J Roach 1
Dale L Bailey 1
1 Faculty of Medicine and Health, University of Sydney, Camperdown, Australia and Department of Medical Oncology, Royal North Shore Hospital, St Leonards, Australia
2 Faculty of Medicine and Health, University of Sydney, Camperdown, Australia
3 Department of Medical Oncology, Royal North Shore Hospital St Leonards, Sydney, NSW, 2065, Australia
4 Department of Nuclear Medicine, Royal North Shore Hospital, St Leonards, Australia
10.22038/aojnmb.2025.83664.1611
Abstract
Objective(s): The phenomenon of peripheral [68Ga]DOTATATE avidity without central avidity (which we have termed a “DONUT") has been observed in neuroendocrine neoplasm (NEN) lesions. There has been speculation as to whether this is due to hypoxia, de-differentiated disease or other causes. The presence of hypoxia may have prognostic and therapeutic implications, and was evaluated in these lesions using the PET hypoxia imaging biomarker [18F]FMISO.
Methods: Prospective pilot study in patients with metastatic NENs with at least one DONUT lesion (central [68Ga]DOTATATE non-avidity). [18F]FDG and [18F]FMISO scans were acquired within 60 days of the [68Ga]DOTATATE PET/CT. [18F]FMISO scans were acquired as a dynamic scan over 20 mins from injection with a delayed image at 2 hours. The dynamic acquisition was analysed quantitatively using a graphical approach yielding parametric images of Influx Rate Constant and Volume of Distribution. [18F]FMISO uptake within the identified DONUT hole on the 2 hr delayed scan was qualitatively scored by two experienced nuclear medicine physicians as: 0 (no uptake), 1 (uptake less than normal liver), 2 (uptake equal to normal liver), or 3 (uptake greater than normal liver).
Results: Ten patients were enrolled with primary sites including pancreas (n=3), small bowel (n=3), rectum (n=2), duodenum (n=1) and lung (n=1).  Six subjects were scored 1, three subjects were scored 2, and one subject was scored 3. All lesions evaluated were located in the liver. Quantitative [18F]FMISO parametric imaging showed evidence of increased uptake rate (Ki) in the photopenic areas of the DONUT lesions in 8/10 subjects. Surrounding uptake rate in normal liver was extremely low. In the qualitative delayed image assessment, only one subject demonstrated [18F]FMISO uptake greater than surrounding normal liver (small bowel primary, G2).
Conclusion: Only one of ten patients with DONUT lesions demonstrated increased [18F]FMISO uptake rate on delayed static imaging. In contrast, dynamic imaging demonstrated increased [18F]FMISO uptake rate in the region of [68Ga]DOTATATE photopenia on 8 of 10 patients. Future research using [18F]FMISO in NEN patients should incorporate dynamic imaging.
Keywords
Hypoxia
[18F]FMISO
[68Ga]DOTATATE
[18F]FDG
PET/CT
Neuroendocrine tumours (NETs)
Subjects
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Asia Oceania Journal of Nuclear Medicine and Biology
Volume 13, Issue 2
July 2025
Pages 117-125