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

Mol Imaging Biol. 2023 Apr;25(2):391-400. doi: 10.1007/s11307-022-01769-3. Epub 2022 Aug 30.

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.

Keywords: Copper; Gliomas; PET/CT; Paediatrics; [64Cu]CuCl2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Child
  • Copper
  • Copper Radioisotopes
  • Female
  • Glioma* / pathology
  • Humans
  • Magnetic Resonance Imaging
  • Positron Emission Tomography Computed Tomography* / methods
  • Positron-Emission Tomography / methods

Substances

  • Copper
  • Copper Radioisotopes