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[18F] MFBG PET imaging: biodistribution, pharmacokinetics, and comparison with [123I] MIBG in neural crest tumour patients

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

Despite its limitations, [123I]MIBG scintigraphy has been the standard for human norepinephrine transporter (hNET) imaging for several decades. Recently, [18F]MFBG has emerged as a promising PET alternative. This prospective trial aimed to evaluate safety, biodistribution, tumour lesion pharmacokinetics, and lesion targeting of [18F]MFBG and perform a head-to-head comparison with [123I]MIBG in neural crest tumour patients.

Methods

Six neural crest tumour patients (4 phaeochromocytoma, 1 paraganglioma, 1 neuroblastoma) with a recent routine clinical [123I]MIBG scintigraphy (interval: − 37–75 days) were included. Adult patients (n = 5) underwent a 30-min dynamic PET, followed by 3 whole-body PET/CT scans at 60, 120, and 180 min after injection of 4 MBq/kg [18F]MFBG. One minor participant underwent a single whole-body PET/CT at 60 min after administration of 2 MBq/kg [18F]MFBG. Normal organ uptake (SUVmean) and lesion uptake (SUVmax; tumour-to-background ratio (TBR)) were measured. Regional distribution volumes (VT) were estimated using a Logan graphical analysis in up to 6 lesions per patient. A lesion-by-lesion analysis was performed to compare detection ratios (DR), i.e. fraction of detected lesions, between [18F]MFBG and [123I]MIBG.

Results

[18F]MFBG was safe and well tolerated. Its biodistribution was overall similar to that of [123I]MIBG, with prominent uptake in the salivary glands, liver, left ventricle wall and adrenals, and mainly urinary excretion. In the phaeochromocytoma subgroup, the median VT was 37.4 mL/cm3 (range: 18.0–144.8) with an excellent correlation between VT and SUVmean at all 3 time points (R2: 0.92–0.94). Mean lesion SUVmax and TBR at 1 h after injection were 19.3 ± 10.7 and 23.6 ± 8.4, respectively. All lesions detected with [123I]MIBG were also observed with [18F]MFBG. The mean DR with [123I]MIBG was significantly lower than with [18F]MFBG (61.0% ± 26.7% vs. 99.8% ± 0.5% at 1 h; p = 0.043).

Conclusion

[18F]MFBG is a promising hNET imaging agent with favourable imaging characteristics and improved lesion targeting compared with [123I]MIBG scintigraphy.

Trial registration

Clinicaltrials.gov: NCT04258592 (Registered: 06 February 2020), EudraCT: 2019-003872-37A.

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Data availability

The datasets generated and/or analysed during the current study are not publicly available which is not approved by the Ethics Committee at UZ/KU Leuven due to patient’s confidentiality issues, but are available from the corresponding author on reasonable request.

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Acknowledgements

The authors want to thank Mr. Kwinten Porters, Mr. Jef Van Loock, Mr. Wies Deckers, Mr. Matthijs Sevenois, Dr. Mathilde Vandamme, Mr. William Leysen, and the PET radiopharmacy team UZ Leuven for their skilled contributions. 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”. Christophe M. Deroose is a Senior Clinical Investigator from the Research Foundation – Flanders (FWO).

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”. Christophe M. Deroose is a senior clinical investigator from the Research Foundation – Flanders (FWO).

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Authors and Affiliations

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

    Elin Pauwels, Kristof Baete, Michel Koole, Sander Jentjens, 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, Kristof Baete, Michel Koole, Sander Jentjens, Kim Serdons, Koen Van Laere & Christophe M. Deroose

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

    Sofie Celen & Guy Bormans

  4. General Medical Oncology, University Hospitals Leuven, Leuven, Belgium

    Oliver Bechter & Paul M. Clement

  5. Endocrinology, University Hospitals Leuven, Leuven, Belgium

    Marie Bex

  6. Paediatric Oncology, University Hospitals Leuven, Leuven, Belgium

    Marleen Renard

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Contributions

The study was designed by EP and CMD. Data collection, including patient-related activities, was done by EP, SC, KB, OB, MB, MR, PMC, SJ, KS, KVL, GB, and CMD. Data analysis and statistics were performed by EP, SC, MK, and CMD. The first draft was written by EP, and all authors revised the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Christophe M. Deroose.

Ethics declarations

Ethical approval

This study was performed in line with the principles of the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Approval was granted by the Ethics Committee Research UZ/KU Leuven (28 January 2020/S63142).

Consent to participate

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

Consent to publish

The authors affirm that human research participants provided informed consent for publication of the images in Figs. 1a and 3.

Competing interests

Paul M. Clement received study budget funds from AstraZeneca and was an advisory board member for AbbVie, AstraZeneca, Bayer, BMS, Daiichi-Sankyo, Leo Pharma, Merck Serono, MSD, Rakuten, Takeda, and Vifor Pharma, outside the scope of the submitted work. Christophe M. Deroose has been a consultant for Terumo, Ipsen, Sirtex, Bayer, and PSI CRO outside the scope of the submitted work. There are no other conflicts of interest.

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Pauwels, E., Celen, S., Baete, K. et al. [18F] MFBG PET imaging: biodistribution, pharmacokinetics, and comparison with [123I] MIBG in neural crest tumour patients. Eur J Nucl Med Mol Imaging 50, 1134–1145 (2023). https://doi.org/10.1007/s00259-022-06046-7

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