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Activity Dose Reduction in 64Cu-DOTATATE PET in Patients with Neuroendocrine Neoplasms: Impact on Image Quality and Lesion Detection Ability

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Abstract

Purpose

Patients with neuroendocrine neoplasms (NEN) engage in lifelong follow-up with frequent somatostatin receptor PET, e.g. [64Cu]Cu-DOTATATE PET, and continued measures to reduce radiation exposures should be in pursued in accordance with the as-low-as-reasonably-achievable (ALARA) principle. We therefore aimed to determine the lowest achievable [64Cu]Cu-DOTATATE dose while maintaining image quality and lesion detection rate.

Procedures

We included scans from 38 patients with NEN referred to routine [64Cu]Cu-DOTATATE PET/CT. Using reconstruction of under-sampled PET list-mode data, we simulated [64Cu]Cu-DOTATATE activity dose-reduced PET equivalents with median [range] 142 MBq [127;157], 95 MBq [85;105], and 48 MBq [42;52], corresponding to 75% (PET75%), 50% (PET50%), and 25% (PET25%) of the full-dose 191 MBq [169;209] (PET100%). Three blinded readers independently assessed image quality (scores 1–5), lesion confidence (scores 0–2), and counted lesions grouped by organs and regions. Number of lesions, proportions of patients with diagnostic image quality (reader-median image quality ≥ 4), diagnostic lesion confidence (reader-median lesion confidence ≥ 1), and per-patient sensitivities and specificities for organ-specific disease on PET75-25% were compared with PET100%.

Results

The median [64Cu]Cu-DOTATATE activity dose could be reduced from 191 to 142 MBq without decline in diagnostic image quality (P = 0.62), diagnostic lesion confidence (P = 1.0), or number of lesions detected in major organs or regions (P = 0.19–0.71). Sensitivity and specificity for detection of liver disease were 100% (26/26 patients) and 100% (12/12), respectively, for both PET75% and PET50%. Overall sensitivity for detection of NEN was 100% (26/26) for both PET75% and PET50%, and overall specificities were 92% (11/12) and 100% (12/12) for PET75 and PET50, respectively. Following dose-blinded post hoc review, the PET75% specificity was adjusted to 100% (12/12).

Conclusions

The [64Cu]Cu-DOTATATE activity dose can be reduced from 191 MBq to at least 142 MBq without losing image quality or lesion detection ability and further reduced to 95 MBq without loss of clinically relevant information.

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Funding

This project received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreements no. 670261 (ERC Advanced Grant) and 668532 (Click-It), the Lundbeck Foundation, the Novo Nordisk Foundation, the Innovation Fund Denmark, the Danish Cancer Society, Arvid Nilsson Foundation, the Neye Foundation, the Research Foundation of Rigshospitalet, the Danish National Research Foundation (grant 126), the Research Council of the Capital Region of Denmark, the Danish Health Authority, the John and Birthe Meyer Foundation, and the Research Council for Independent Research. Andreas Kjaer is a Lundbeck Foundation Professor.

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Authors and Affiliations

  1. Department of Clinical Physiology, Nuclear Medicine and PET & Cluster for Molecular Imaging, Copenhagen University Hospital – Rigshospitalet & Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark

    Mathias Loft, Esben A. Carlsen, Camilla B. Johnbeck, Christoffer V. Jensen, Flemming L. Andersen, Peter Oturai & Andreas Kjaer

  2. ENETS Neuroendocrine Tumor Center of Excellence, Copenhagen University Hospital – Rigshospitalet, Copenhagen, Denmark

    Mathias Loft, Esben A. Carlsen, Camilla B. Johnbeck, Seppo W. Langer, Peter Oturai, Ulrich Knigge & Andreas Kjaer

  3. Department of Oncology, Copenhagen University Hospital – Rigshospitalet, Copenhagen, Denmark

    Seppo W. Langer

  4. Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark

    Seppo W. Langer

  5. Departments of Clinical Endocrinology and Surgical Gastroenterology, Copenhagen University Hospital – Rigshospitalet, Copenhagen, Denmark

    Ulrich Knigge

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  1. Mathias Loft
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  2. Esben A. Carlsen
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Contributions

Conceptualization: M.L., C.B.J., E.A.C., F.L.A., and A.K.; formal analysis: M.L., C.B.J., E.A.C., and A.K.; investigation: M.L., C.B.J., E.A.C., and C.V.J.; methodology: M.L., C.B.J., E.A.C., C.V.J., F.L.A., and A.K.; resources: P.O., S.W.L., F.L.A., U.K., and A.K.; software: C.V.J.; supervision: U.K. and A.K.; visualization: M.L.; writing—original draft preparation: M.L.; writing—review and editing: all authors. All authors have read and agreed to the final version of the manuscript.

Corresponding author

Correspondence to Andreas Kjaer.

Ethics declarations

Ethical Approval

This research study was conducted retrospectively in accordance with the 1964 Helsinki declaration and its later amendments or comparable ethical standards following approval by the Danish Patient Safety Authority (Ref 31–1521-453) according to Danish regulations. For this type of study, formal consent is not required. All the procedures being performed were part of the patient’s routine care.

Conflict of Interest

U.K. and A.K. are inventors/holds intellectual property rights on a patent covering [64Cu]Cu-DOTATATE. All other authors declare that they have no conflict of interest.

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Loft, M., Carlsen, E.A., Johnbeck, C.B. et al. Activity Dose Reduction in 64Cu-DOTATATE PET in Patients with Neuroendocrine Neoplasms: Impact on Image Quality and Lesion Detection Ability. Mol Imaging Biol 24, 600–611 (2022). https://doi.org/10.1007/s11307-022-01706-4

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  • DOI: https://doi.org/10.1007/s11307-022-01706-4

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