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.

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., Al-Nahhas, A., Saleem, A., Huiban, M., Janisch, R., Frilling, A., Sharma, R., & 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