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Clinical translation of a click-labeled 18F-octreotate radioligand for imaging neuroendocrine tumors

Dubash, Suraiya R.; Nicholas Keat; Mapelli, Paola; Twyman, Frazer; Carroll, Laurence; Kozlowski, Kasia; Al-Nahhas, Adil; Saleem, Azeem; Huiban, Mickael; Janisch, Ryan; Frilling, Andrea; Sharma, Rohini; Aboagye, Eric O.

Authors

Suraiya R. Dubash

Nicholas Keat

Paola Mapelli

Frazer Twyman

Laurence Carroll

Kasia Kozlowski

Adil Al-Nahhas

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Dr Azeem Saleem A.Saleem@hull.ac.uk
Reader and Honorary Consultant in Clinical Oncology

Mickael Huiban

Ryan Janisch

Andrea Frilling

Rohini Sharma

Eric O. Aboagye



Abstract

© 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc. We conducted the first-in-human study of 18F-fluoroethyl triazole [Tyr3] octreotate (18F-FET-βAG-TOCA) in patients with neuroendocrine tumors (NETs) to evaluate biodistribution, dosimetry, and safety. Despite advances in clinical imaging, detection and quantification of NET activity remains a challenge, with no universally accepted imaging standard. Methods: Nine patients were enrolled. Eight patients had sporadic NETs, and 1 had multiple endocrine neoplasia type 1 syndrome. Patients received 137-163 MBq (mean ± SD, 155.7 ± 8 MBq) of 18F-FET-βAG-TOCA. Safety data were obtained during and 24 h after radioligand administration. Patients underwent detailed wholebody PET/CT multibed scanning over 4 h with sampling of venous bloods for radioactivity and radioactive metabolite quantification. Regions of interest were defined to derive individual and mean organ residence times; effective dose was calculated with OLINDA 1.1. Results: All patients tolerated 18F-FET-βAG-TOCA with no adverse events. Over 60% parent radioligand was present in plasma at 60 min. High tumor (primary and metastases)-to-background contrast images were observed. Physiologic distribution was seen in the pituitary, salivary glands, thyroid, and spleen, with low background distribution in the liver, an organ in which metastases commonly occur. The organs receiving highest absorbed dose were the gallbladder, spleen, stomach, liver, kidneys, and bladder. The calculated effective dose over all subjects (mean ± SD) was 0.029 ± 0.004 mSv/MBq. Conclusion: The favorable safety, imaging, and dosimetric profile makes 18F-FET-βAGTOCA a promising candidate radioligand for staging and management of NETs. Clinical studies in an expanded cohort are ongoing to clinically qualify this agent.

Citation

Dubash, S. R., Nicholas Keat, , Mapelli, P., Twyman, F., Carroll, L., Kozlowski, K., …Aboagye, E. O. (2016). Clinical translation of a click-labeled 18F-octreotate radioligand for imaging neuroendocrine tumors. Journal of nuclear medicine, 57(8), 1207-1213. https://doi.org/10.2967/jnumed.115.169532

Journal Article Type Article
Acceptance Date Jan 29, 2016
Online Publication Date May 12, 2016
Publication Date Aug 1, 2016
Deposit Date Jan 25, 2021
Publicly Available Date Jan 26, 2021
Journal Journal of Nuclear Medicine
Print ISSN 0161-5505
Electronic ISSN 2159-662X
Publisher Society of Nuclear Medicine
Peer Reviewed Peer Reviewed
Volume 57
Issue 8
Pages 1207-1213
DOI https://doi.org/10.2967/jnumed.115.169532
Keywords Neuroendocrine; 18F-fluroethyl [Tyr3] octreotate analog; PET/CT imaging
Public URL https://hull-repository.worktribe.com/output/3630164
Publisher URL https://jnm.snmjournals.org/content/57/8/1207
Related Public URLs https://spiral.imperial.ac.uk/handle/10044/1/29955

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Copyright Statement
COPYRIGHT © 2016 by the Society of Nuclear Medicine and Molecular
Imaging, Inc.








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