Evaluation of [18F]Fluoroethyl Triazole Labelled [Tyr3]-Octreotate Analogues for the Imaging of Neuroendocrine Tumours.

NCT06456723 | Completed Phase 1 Results

• 1 other identifier: 13HH0807
• Study Type: interventional
• Target: 56
• Locations: 0 countries
• Sites: N/A

Brief Summary

Radiolabelled somatostatin analogs are invaluable in the diagnosis and treatment of neuroendocrine tumours (NET). The most common positron emission tomography (PET) radiotracers used for the visualisation of NET are radiolabelled somatostatin analogs (SSAs) labelled with \[68Ga\]Ga-DOTA-peptides. However, \[68Ga\]Ga-DOTA-peptide radiolabelled SSAs have significant limitations in terms of accessibility and low throughput. The team at Imperial College London developed a novel radiotracer, \[18F\]fluoroethyl triazole labelled \[Tyr3\]-Octreotate analogue (\[18F\]-FET-βAG-TOCA), in an attempt to overcome these limitations. The FETONET study was designed to have 3 parts. The FETONET study was designed to have 3 parts. Part A evaluated the biodistribution, dosimetry and safety of \[18F\]FET-βAG-TOCA. Uptake was assessed at multiple time points over a 4 hour period. The data was analysed and an optimal imaging time point determined. Part B of the FETONET study involved the performance of whole body static \[18F\]FET-βAG-TOCA PET-CT imaging, at the optimal time point previously established, within a larger cohort of patients. Part C comprised a prospective non-inferiority study that analysed the \[18F\]FET-βAG-TOCA PET/CT data collected within Part A \& Part B and compared this to standard of care \[Ga68\]Ga-DOTA-peptide PET-CT imaging.

Conditions

Neuroendocrine Tumors

Keywords

Positron Emission Tomography

Outcome Measures

Primary Outcomes (3)

• To Determine the Biodistribution of [18F] Following Single I.V Administration of [18F]-FET-βAG-TOCA Injection in Patients With a Histological Diagnosis of NET.

  Mean residence time (MRT) was used to characterise the biodistribution of \[18F\]-FET-βAG-TOCA throughout the body. Mean residence time is a pharmacokinetic/uptake parameter that describes the average length of time a radiotracer resides within the body, or a particular organ, before being eliminated. Understanding MRT helps researchers to determine how long a radiotracer remains in the system, which is crucial for drug dosing, therapeutic efficacy, and potential toxicity assessment.

  Baseline (on day of scan over 4 hours)

• To Calculate the Effective Dose (ED) of [18F]-FET-βAG-TOCA

  Effective dose is an estimate of the overall risk of potential harm from exposure to ionising radiation. ED takes into account, the absorbed dose to all organs of the body, the relative harm level of the radiation and the sensitivities of each organ to radiation. ED may help in understanding the risk of potential long-term health effects from radiation exposure, such as the risk of developing cancer later in life. The unit of measure for ED is millisievert per megabecquerel (mSv/MBq), which refers to the effective dose (amount of radiation absorbed by the body) per unit of activity administered.

  Baseline (on the day of the scan over 4 hours)

• To Assess Tumoural Uptake of [18F]-FET-βAG-TOCA

  Standardised uptake value (SUV) is a semiquantitative measurement of radiotracer uptake in tissue. It is a ratio that compares the activity concentration in a specific region of interest to the activity concentration in the whole body. SUVmax is the highest value of the SUV measured within a region of interest.

  Baseline (on the scan day over 4 hours)

Secondary Outcomes (2)

• To Compare the Diagnostic Efficacy of [18F]-FET-βAG-TOCA PET/CT With Standard of Care Somatostatin Receptor Imaging in Patients With a Histological Diagnosis of NET.

  [68Ga]Ga-DOTA-peptide PET/CT imaging performed within 6 months of the [18F]-FET-βAG-TOCA PET/CT scan.

• Comparison of [18F]-FET-βAG-TOCA PET/CT Scan and Central Review (Nuclear Medicine and Radiology Physician Experts) of All Imaging Received.

  [68Ga]Ga-DOTA-peptide PET/CT imaging assessed within 6 months of the [18F]-FET-βAG-TOCA PET/CT scan.

Study Arms (2)

Part A: [18F]-FET-βAG-TOCA-PET/CT performed in patients with histologically-confirmed NET.

EXPERIMENTAL

Patients with histologically-confirmed neuroendocrine tumours (NET) enrolled into Part A of the FETONET study underwent whole-body dynamic \[18F\]FET-βAG-TOCA imaging at multiple time points over a 4 hour period, with sampling of venous bloods for radioactivity and radioactive metabolite quantification.

Drug: [18F]-FET-βAG-TOCA

Part B: [18F]FET-βAG-TOCA PET/CT compared with [68Ga]Ga-DOTA-peptide PET/CT in patients with NET.

EXPERIMENTAL

Patients with histologically confirmed neuroendocrine tumours (NET) underwent PET/CT imaging with both \[18F\]FET-βAG-TOCA and \[68Ga\]Ga-DOTA-peptide. The two PET/CT scans were performed within a 6-month time period. Whole-body static \[18F\]FET-βAG-TOCA PET/CT scan performed at 50 minutes post radiotracer injection.

Drug: [18F]-FET-βAG-TOCA

Interventions

[18F]-FET-βAG-TOCA DRUG

Single I.V. administration of a \[18F\]fluoroethyl triazole \[Tyr3\]Octreotate (\[18F\]-FET-βAG-TOCA). Patients will receive a maximum injected dose of 370MBq and will subsequently undergo PET/CT imaging.

Part A: [18F]-FET-βAG-TOCA-PET/CT performed in patients with histologically-confirmed NET.; Part B: [18F]FET-βAG-TOCA PET/CT compared with [68Ga]Ga-DOTA-peptide PET/CT in patients with NET.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent
• Age ≥ 18 years
• Histological diagnosis of NET of any site, except where ENETS criteria does not mandate histology for confirmation of diagnosis or patients who have a positive 68Gallium-peptide scan in whom NET diagnosis is pre-operatively definitive.
• Locally advanced or metastatic disease.
• Eastern Cooperative Oncology Group (ECOG) performance status of \<2 (appendix A).
• Life expectancy \> 3 months.
• Measurable disease defined as a lesion that can be accurately measured in at least one dimension with the longest diameter ≥10mm using conventional techniques.
• Somatostatin receptor imaging within 6 months. (if patient does not have somatostatin receptor imaging they may also be included provided they have measurable disease (≥10mm) on conventional imaging.
• Adequate organ system function as defined within Table 1.

You may not qualify if:

• Patients received chemotherapy within 3 weeks of study.
• Patients received radiotherapy within 4 weeks of study.
• Active uncontrolled infections, gastrointestinal disease, haemolysis or any serious co-existing medical illness.
• Psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.
• Pregnant or lactating women.
• Females of childbearing potential who are unwilling to avoid pregnancy, for the duration of the study.
• Presence of any underlying medical conditions which in the investigators opinion would make the patients unsuitable for treatment.
• Patient not expected to be able to tolerate the scanning sessions.

Sponsors & Collaborators

• Imperial College London: lead
• Imperial College Healthcare NHS Trust: collaborator
• Royal Marsden NHS Foundation Trust: collaborator
• University of Manchester: collaborator
• The Christie NHS Foundation Trust: collaborator
• Invicro: collaborator
• Newcastle University: collaborator

Related Publications (2)

• Dubash SR, Keat N, Mapelli P, Twyman F, Carroll L, Kozlowski K, Al-Nahhas A, Saleem A, Huiban M, Janisch R, Frilling A, Sharma R, Aboagye EO. Clinical Translation of a Click-Labeled 18F-Octreotate Radioligand for Imaging Neuroendocrine Tumors. J Nucl Med. 2016 Aug;57(8):1207-13. doi: 10.2967/jnumed.115.169532. Epub 2016 May 12.

  PMID: 27173162 BACKGROUND

• Dubash S, Barwick TD, Kozlowski K, Rockall AG, Khan S, Khan S, Yusuf S, Lamarca A, Valle JW, Hubner RA, McNamara MG, Frilling A, Tan T, Wernig F, Todd J, Meeran K, Pratap B, Azeem S, Huiban M, Keat N, Lozano-Kuehne JP, Aboagye EO, Sharma R. Somatostatin Receptor Imaging with [18F]FET-betaAG-TOCA PET/CT and [68Ga]Ga-DOTA-Peptide PET/CT in Patients with Neuroendocrine Tumors: A Prospective, Phase 2 Comparative Study. J Nucl Med. 2024 Feb 8;65(3):416-22. doi: 10.2967/jnumed.123.266601. Online ahead of print.

  PMID: 38331457 RESULT

MeSH Terms

Conditions

Neuroendocrine Tumors

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue

Results Point of Contact

• Title: Professor Rohini Sharma
• Organization: Imperial College London

r.sharma@imperial.ac.uk

0203 313 3720

Study Officials

• Rohini Sharma

  Imperial College London

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 28, 2024
• First Posted: June 13, 2024
• Study Start: May 14, 2014
• Primary Completion: October 17, 2018
• Study Completion: October 17, 2018
• Last Updated: May 1, 2025
• Results First Posted: May 1, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share