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

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...

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Main Authors: David Chan, Alice Conner, Nick Pavlakis, Elizabeth Bailey, Alireza Aslani, Kathy Willowson, Connie Diakos, Elizabeth Bernard, Stephen Clarke, Alexander Engel, Paul Roach, Dale Bailey
Format: Article
Language:English
Published: Mashhad University of Medical Sciences 2025-07-01
Series:Asia Oceania Journal of Nuclear Medicine and Biology
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Online Access:https://aojnmb.mums.ac.ir/article_25553_388a319f033dd0a7df02c795cb7fbac3.pdf
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author David Chan
Alice Conner
Nick Pavlakis
Elizabeth Bailey
Alireza Aslani
Kathy Willowson
Connie Diakos
Elizabeth Bernard
Stephen Clarke
Alexander Engel
Paul Roach
Dale Bailey
author_facet David Chan
Alice Conner
Nick Pavlakis
Elizabeth Bailey
Alireza Aslani
Kathy Willowson
Connie Diakos
Elizabeth Bernard
Stephen Clarke
Alexander Engel
Paul Roach
Dale Bailey
author_sort David Chan
collection DOAJ
description 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.
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spelling doaj-art-bef359bc17134755abb7c7b6cf6cf8b42025-08-20T03:26:33ZengMashhad University of Medical SciencesAsia Oceania Journal of Nuclear Medicine and Biology2322-57182322-57262025-07-0113211712510.22038/aojnmb.2025.83664.161125553[18F]FMISO PET in metastatic neuroendocrine tumours: a pilot studyDavid Chan0Alice Conner1Nick Pavlakis2Elizabeth Bailey3Alireza Aslani4Kathy Willowson5Connie Diakos6Elizabeth Bernard7Stephen Clarke8Alexander Engel9Paul Roach10Dale Bailey11Faculty of Medicine and Health, University of Sydney, Camperdown, Australia and Department of Medical Oncology, Royal North Shore Hospital, St Leonards, AustraliaFaculty of Medicine and Health, University of Sydney, Camperdown, AustraliaFaculty of Medicine and Health, University of Sydney, Camperdown, Australia and Department of Medical Oncology, Royal North Shore Hospital, St Leonards, AustraliaDepartment of Medical Oncology, Royal North Shore Hospital St Leonards, Sydney, NSW, 2065, AustraliaDepartment of Medical Oncology, Royal North Shore Hospital St Leonards, Sydney, NSW, 2065, AustraliaDepartment of Nuclear Medicine, Royal North Shore Hospital, St Leonards, AustraliaFaculty of Medicine and Health, University of Sydney, Camperdown, Australia and Department of Medical Oncology, Royal North Shore Hospital, St Leonards, AustraliaDepartment of Nuclear Medicine, Royal North Shore Hospital, St Leonards, AustraliaFaculty of Medicine and Health, University of Sydney, Camperdown, Australia and Department of Medical Oncology, Royal North Shore Hospital, St Leonards, AustraliaFaculty of Medicine and Health, University of Sydney, Camperdown, AustraliaFaculty of Medicine and Health, University of Sydney, Camperdown, Australia and Department of Medical Oncology, Royal North Shore Hospital, St Leonards, AustraliaFaculty of Medicine and Health, University of Sydney, Camperdown, Australia and Department of Medical Oncology, Royal North Shore Hospital, St Leonards, AustraliaObjective(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.https://aojnmb.mums.ac.ir/article_25553_388a319f033dd0a7df02c795cb7fbac3.pdfhypoxia[18f]fmiso[68ga]dotatate[18f]fdgpet/ctneuroendocrine tumours (nets)
spellingShingle David Chan
Alice Conner
Nick Pavlakis
Elizabeth Bailey
Alireza Aslani
Kathy Willowson
Connie Diakos
Elizabeth Bernard
Stephen Clarke
Alexander Engel
Paul Roach
Dale Bailey
[18F]FMISO PET in metastatic neuroendocrine tumours: a pilot study
Asia Oceania Journal of Nuclear Medicine and Biology
hypoxia
[18f]fmiso
[68ga]dotatate
[18f]fdg
pet/ct
neuroendocrine tumours (nets)
title [18F]FMISO PET in metastatic neuroendocrine tumours: a pilot study
title_full [18F]FMISO PET in metastatic neuroendocrine tumours: a pilot study
title_fullStr [18F]FMISO PET in metastatic neuroendocrine tumours: a pilot study
title_full_unstemmed [18F]FMISO PET in metastatic neuroendocrine tumours: a pilot study
title_short [18F]FMISO PET in metastatic neuroendocrine tumours: a pilot study
title_sort 18f fmiso pet in metastatic neuroendocrine tumours a pilot study
topic hypoxia
[18f]fmiso
[68ga]dotatate
[18f]fdg
pet/ct
neuroendocrine tumours (nets)
url https://aojnmb.mums.ac.ir/article_25553_388a319f033dd0a7df02c795cb7fbac3.pdf
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