title: Clinical Translation of a Click-Labeled 18F-Octreotate Radioligand for Imaging Neuroendocrine Tumors.
abstract: We conducted the first-in-human study of (18)F-fluoroethyl triazole [Tyr(3)] 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.
  
  
  
  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 (18)F-FET-βAG-TOCA. Safety data were obtained during and 24 h after radioligand administration. Patients underwent detailed whole-body 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.
  
  
  
  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. 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.
  
  
  
  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.
authors.affiliation: Department of Surgery and Cancer, Imperial College London, London, United Kingdom.
authors.forename: Suraiya R
authors.initials: SR
authors.lastname: Dubash
authors.affiliation: Imanova Centre for Imaging Sciences, London, United Kingdom.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Keat
authors.affiliation: Department of Surgery and Cancer, Imperial College London, London, United Kingdom.
authors.forename: Paola
authors.initials: P
authors.lastname: Mapelli
authors.affiliation: Department of Surgery and Cancer, Imperial College London, London, United Kingdom.
authors.forename: Frazer
authors.initials: F
authors.lastname: Twyman
authors.affiliation: Department of Surgery and Cancer, Imperial College London, London, United Kingdom.
authors.forename: Laurence
authors.initials: L
authors.lastname: Carroll
authors.affiliation: Department of Surgery and Cancer, Imperial College London, London, United Kingdom.
authors.forename: Kasia
authors.initials: K
authors.lastname: Kozlowski
authors.affiliation: Department of Radiology/Nuclear Medicine, Imperial College Healthcare NHS Trust, London, United Kingdom; and.
authors.forename: Adil
authors.initials: A
authors.lastname: Al-Nahhas
authors.affiliation: Imanova Centre for Imaging Sciences, London, United Kingdom.
authors.forename: Azeem
authors.initials: A
authors.lastname: Saleem
authors.affiliation: Imanova Centre for Imaging Sciences, London, United Kingdom.
authors.forename: Mickael
authors.initials: M
authors.lastname: Huiban
authors.affiliation: Imanova Centre for Imaging Sciences, London, United Kingdom.
authors.forename: Ryan
authors.initials: R
authors.lastname: Janisch
authors.affiliation: Department of Surgery, Imperial College Healthcare NHS Trust, London, United Kingdom.
authors.forename: Andrea
authors.initials: A
authors.lastname: Frilling
authors.affiliation: Department of Surgery and Cancer, Imperial College London, London, United Kingdom.
authors.forename: Rohini
authors.initials: R
authors.lastname: Sharma
authors.affiliation: Department of Surgery and Cancer, Imperial College London, London, United Kingdom eric.aboagye@imperial.ac.uk.
authors.forename: Eric O
authors.initials: EO
authors.lastname: Aboagye
mesh_terms: D000328:Adult; D000368:Aged; D057930:Click Chemistry / Q000379:methods; D005260:Female; D005462:Fluorine Radioisotopes / Q000737:chemistry*; D006801:Humans; D007553:Isotope Labeling / Q000379:methods*; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors; D015282:Octreotide; D000072078:Positron Emission Tomography Computed Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; D015282:Octreotide
keywords: 18F-fluroethyl [Tyr3] octreotate analog; PET/CT imaging; neuroendocrine