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Diagnostic and Dosimetry Features of [64Cu]CuCl2 in High-Grade Paediatric Infiltrative Gliomas

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Abstract

Purpose of the Report

Paediatric diffuse high-grade gliomas (PDHGG) are rare central nervous system neoplasms lacking effective therapeutic options. Molecular imaging of tumour metabolism might identify novel diagnostic/therapeutic targets. In this study, we evaluated the distribution and the dosimetry aspects of [64Cu]CuCl2 in PDHGG subjects, as copper is a key element in cellular metabolism whose turnover may be increased in tumour cells.

Material and Methods

Paediatric patients with PDHGG were prospectively recruited. [64Cu]CuCl2 PET/CT was performed 1 h after tracer injection; if the scan was positive, it was repeated 24 and 72 h later. Lesion standardised uptake value (SUV) and target-to-background ratio (TBR) were calculated. Tumour and organ dosimetry were computed using the MIRD algorithm. Each patient underwent an MRI scan, including FLAIR, T2-weighted and post-contrast T1-weighted imaging.

Results

Ten patients were enrolled (median age 9, range 6–16 years, 6 females). Diagnoses were diffuse midline gliomas (n = 8, 5 of which with H3K27 alterations) and diffuse hemispheric gliomas (n = 2). Six patients had visible tracer uptake (SUV: 1.0 ± 0.6 TBR: 5 ± 3.1). [64Cu]CuCl2 accumulation was always concordant with MRI contrast enhancement and was higher in the presence of radiological signs of necrosis. SUV and TBR progressively increased on the 24- and 72-h acquisitions (p < 0.05 and p < 0.01, respectively). The liver and the abdominal organs received the highest non-target dose.

Conclusions

[64Cu]CuCl2 is a well-tolerated radiotracer with reasonably favourable dosimetric properties, showing selective uptake in tumour areas with visible contrast enhancement and necrosis, thus suggesting that blood–brain barrier damage is a pre-requisite for its distribution to the intracranial structures. Moreover, tracer uptake showed an accumulating trend over time. These characteristics could deserve further analysis, to determine whether this radiopharmaceutical might have a possible therapeutic role as well.

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Funding

This work was supported by the Italian Ministry of Health and by Regione Liguria “Ricerca Finalizzata di Rete NET-2019–12371188 GLI-HOPE”.

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Authors and Affiliations

  1. Department of Nuclear Medicine, E.O. Ospedali Galliera, Galliera Hospital, Mura delle Cappuccine 14, 16128, Genoa, Italy

    Francesco Fiz, Gianluca Bottoni, Martina Ugolini & Arnoldo Piccardo

  2. Medical Physics Department, E.O. Galliera Hospital, Genoa, Italy

    Sergio Righi & Alessio Cirone

  3. Nuclear Medicine Unit/Imaging Department, IRCCS Bambino Gesù Children’s Hospital, Rome, Italy

    Maria Carmen Garganese

  4. Neuro-Oncology Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy

    Antonio Verrico, Claudia Milanaccio & Maria Luisa Garrè

  5. Neuroradiology Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy

    Andrea Rossi & Antonia Ramaglia

  6. Department of Health Sciences (DISSAL), University of Genoa, Genoa, Italy

    Andrea Rossi

  7. Neuro-Oncology Unit, Department of Paediatric Haematology/Oncology, Cell Therapy, Gene Therapies and Hemopoietic Transplant, Bambino Gesù Children’s Hospital, IRCCS, 00165, Rome, Italy

    Angela Mastronuzzi & Antonella Cacchione

  8. Pediatric Oncology Unit, AORN Santobono-Pausilipon Hospital, Naples, Italy

    Massimo Eraldo Abate

  9. Imaging Department, Neuroradiology Unit, IRCCS Bambino Gesù Children’s Hospital, Rome, Italy

    Carlo Gandolfo & Giovanna Stefania Colafati

  10. Department of Neurosciences, University of Turin, Turin, Italy

    Giovanni Morana

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  1. Francesco Fiz
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Correspondence to Francesco Fiz.

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Giovanni Morana and Arnoldo Piccardo share senior co-authorship.

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Fiz, F., Bottoni, G., Ugolini, M. et al. Diagnostic and Dosimetry Features of [64Cu]CuCl2 in High-Grade Paediatric Infiltrative Gliomas. Mol Imaging Biol 25, 391–400 (2023). https://doi.org/10.1007/s11307-022-01769-3

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