Clinical Translation of a Click-Labeled 18F-Octreotate Radioligand for Imaging Neuroendocrine Tumors

We conducted the first-in-human study of (18)F-fluoroethyl triazole [Tyr3] octreotate ((18)F-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 NET and one had multiple endocrine neoplasia type 1 (MEN1) syndrome. Patients received 137-163MBq (mean 155.7± 8 MBq) of (18)F-FET-βAG-TOCA. Safety data were obtained during and 24 h after radioligand administration. Patients underwent detailed whole body PET-CT multi-bed 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 (ED) was calculated with OLINDA 1.1. Results All patients tolerated (18)F-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. Physiological distribution was seen in pituitary, salivary, thyroid and spleen, with low background distribution in liver, an organ where metastases commonly occur. The organs receiving highest absorbed dose were gallbladder, spleen, stomach, liver, kidneys and bladder. The calculated ED over all subjects (mean ± SD) was 0.029 ± 0.004 mSv/MBq. Conclusion The favorable safety, imaging and dosimetric profile makes (18)F-FET-βAG-TOCA a promising candidate radioligand for staging and management of NETs. Clinical studies in an expanded cohort are ongoing to clinically qualify this agent