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[18F]AlF-NOTA-octreotide PET imaging: biodistribution, dosimetry and first comparison with [68Ga]Ga-DOTATATE in neuroendocrine tumour patients

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Abstract

Purpose

The widespread use of gallium-68-labelled somatostatin analogue (SSA) PET, the current standard for somatostatin receptor (SSTR) imaging, is limited by practical and economic challenges that could be overcome by a fluorine-18-labelled alternative, such as the recently introduced [18F]AlF-NOTA-octreotide ([18F]AlF-OC). This prospective trial aimed to evaluate safety, dosimetry, biodistribution, pharmacokinetics and lesion targeting of [18F]AlF-OC and perform the first comparison with [68Ga]Ga-DOTATATE in neuroendocrine tumour (NET) patients.

Methods

Six healthy volunteers and six NET patients with a previous clinical [68Ga]Ga-DOTATATE PET were injected with an IV bolus of 4 MBq/kg [18F]AlF-OC. Healthy volunteers underwent serial whole-body PET scans from time of tracer injection up to 90 min post-injection, with an additional PET/CT at 150 and 300 min post-injection. In patients, a 45-min dynamic PET was acquired and three whole-body PET scans at 60, 90 and 180 min post-injection. Absorbed organ doses and effective doses were calculated using OLINDA/EXM. Normal organ uptake (SUVmean) and tumour lesion uptake (SUVmax and tumour-to-background ratio (TBR)) were measured. A lesion-by-lesion analysis was performed and the detection ratio (DR), defined as the fraction of detected lesions was determined for each tracer.

Results

[18F]AlF-OC administration was safe and well tolerated. The highest dose was received by the spleen (0.159 ± 0.062 mGy/MBq), followed by the urinary bladder wall (0.135 ± 0.046 mGy/mBq) and the kidneys (0.070 ± 0.018 mGy/MBq), in accordance with the expected SSTR-specific uptake in the spleen and renal excretion of the tracer. The effective dose was 22.4 ± 4.4 μSv/MBq. The physiologic uptake pattern of [18F]AlF-OC was comparable to [68Ga]Ga-DOTATATE. Mean tumour SUVmax was lower for [18F]AlF-OC (12.3 ± 6.5 at 2 h post-injection vs. 18.3 ± 9.5; p = 0.03). However, no significant differences were found in TBR (9.8 ± 6.7 at 2 h post-injection vs. 13.6 ± 11.8; p = 0.35). DR was high and comparable for both tracers (86.0% for [68Ga]Ga-DOTATATE vs. 90.1% for [18F]AlF-OC at 2 h post-injection; p = 0.68).

Conclusion

[18F]AlF-OC shows favourable kinetic and imaging characteristics in patients that warrant further head-to-head comparison to validate [18F]AlF-OC as a fluorine-18-labelled alternative for gallium-68-labelled SSA clinical PET.

Trial registration

Clinicaltrials.gov: NCT03883776, EudraCT: 2018-002827-40

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Acknowledgements

The authors explicitly want to thank Mr. Kwinten Porters and Mr. Jef Van Loock for their contributions to the scanning and data handling, and the PET radiopharmacy team and medical physics team of UZ Leuven for their skilled contributions.

Funding

This research was funded by the project from “Kom op tegen Kanker”: “PET/MR imaging of the norepinephrine transporter and somatostatin receptor in neural crest and neuroendocrine tumours for better radionuclide therapy selection” and received support from Research Foundation – Flanders (FWO) (G0D8817N). Frederik Cleeren is a Postdoctoral Fellow of FWO (12R3119N). Christophe M. Deroose is a Senior Clinical Investigator at FWO.

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Authors and Affiliations

  1. Nuclear Medicine, University Hospitals Leuven, Campus Gasthuisberg, Herestraat 49, BE-3000, Leuven, Belgium

    Elin Pauwels, Michel Koole, Kim Serdons, Koen Van Laere & Christophe M. Deroose

  2. Nuclear Medicine and Molecular Imaging, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium

    Elin Pauwels, Michel Koole, Kim Serdons, Koen Van Laere & Christophe M. Deroose

  3. Radiopharmaceutical Research, Department of Pharmacy and Pharmacology, KU Leuven, Leuven, Belgium

    Frederik Cleeren, Térence Tshibangu & Guy Bormans

  4. Digestive Oncology, University Hospitals Leuven, Leuven, Belgium

    Jeroen Dekervel, Eric Van Cutsem & Chris Verslype

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  1. Elin Pauwels
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  2. Frederik Cleeren
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Corresponding author

Correspondence to Christophe M. Deroose.

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Conflict of interest

Eric Van Cutsem has received research grants and personal fees for consultancy from Amgen, Bayer, Boehringer Ingelheim, Celgene, Ipsen, Lilly, Roche, Merck Sharp & Dohme, Merck KGaA, Novartis, Roche and Servier. Chris Verslype has received research grants and performed consultancy services for Novartis and Ipsen. Koen Van Laere has performed consultancy services and contract research through KU Leuven for GE Healthcare, Merck, Janssen Pharmaceuticals, UCB, Syndesi Therapeutics, Curasen, Celgene and Eikonizo. Guy Bormans has performed funded contract research through KU Leuven with Eikonizo, Merck, Celgene, Janssen Pharmaceuticals, Lundbeck and UCB. Christophe M. Deroose has been a consultant through KU Leuven for Novartis, Terumo, AAA, Ipsen, Sirtex, Bayer outside the scope of the submitted work. There are no other conflicts of interest.

Ethical approval

All procedures performed in the study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee (Ethische Commissie Onderzoek UZ/KU Leuven S61727) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Written informed consent was obtained from all individual participants included in the study.

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Pauwels, E., Cleeren, F., Tshibangu, T. et al. [18F]AlF-NOTA-octreotide PET imaging: biodistribution, dosimetry and first comparison with [68Ga]Ga-DOTATATE in neuroendocrine tumour patients. Eur J Nucl Med Mol Imaging 47, 3033–3046 (2020). https://doi.org/10.1007/s00259-020-04918-4

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