<p>The incidence of Intracranial Metastatic Disease (IMD) continues to increase in part due to improvements in systemic therapy resulting in durable control of extra-cranial disease (ECD). Contrast-enhanced Magnetic Resonance Imaging (CE-MRI) is the preferred method for imaging IMD, but has limitations particularly in follow-up surveillance scans to optimise patient care. We investigate a new diagnostic approach of hybrid ([<sup>18</sup>]F]fluoropivalate (FPIA) Positron Emission Tomography-multiparametric MRI (PET-<i>mp</i>MRI), in 12 treatment-naïve and 10 stereotactic radiosurgery (SRS)-treated patients (± combination therapy within 4–8 weeks). High FPIA uptake was seen in all IMD compared to contralateral white matter, regardless of ECD tumour-of-origin (<i>p</i> = 0.0001) and FPIA-PET volumes extended beyond CE-MRI volumes in treatment-naïve but not SRS-treated tumours. Patients with maximum PET Standardised Uptake Value, (SUVmax) ≥ 2.0 showed particularly short overall-survival (median 4 v 15 months, <i>p</i> = 0.0136), while CE-MRI was uninformative regarding outcome; a PET-<i>mp</i>MRI grade-measure also provided non-invasive prediction of overall-survival, warranting larger studies of PET-<i>mp</i>MRI. Independent metabolomics analyses were consistent with shared adaptation of IMD to utilise or accumulate monocarboxylates and acylcarnitines, respectively, providing a common phenotypic basis to FPIA-PET. Reprogrammed monocarboxylate metabolism-related FPIA-PET provides new insights into annotating IMD, to be expounded in future opportunities for therapy decisions for the growing number of cancer patients with IMD <i>[Trial registration reference: Clinicaltrials.gov NCT04807582; 3rd November 2021</i>,<i> retrospectively registered]</i>.</p>

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A hybrid [18F]fluoropivalate PET-multiparametric MRI to detect and characterise brain tumour metastases based on a permissive environment for monocarboxylate transport

  • S. Islam,
  • M. Inglese,
  • P. Aravind,
  • T. D. Barwick,
  • F. Mauri,
  • L. McLeavy,
  • E. Årstad,
  • J. Wang,
  • I. Puccio,
  • L. Hung,
  • H. Lu,
  • K. O’Neill,
  • A. D. Waldman,
  • M. Williams,
  • E. O. Aboagye

摘要

The incidence of Intracranial Metastatic Disease (IMD) continues to increase in part due to improvements in systemic therapy resulting in durable control of extra-cranial disease (ECD). Contrast-enhanced Magnetic Resonance Imaging (CE-MRI) is the preferred method for imaging IMD, but has limitations particularly in follow-up surveillance scans to optimise patient care. We investigate a new diagnostic approach of hybrid ([18]F]fluoropivalate (FPIA) Positron Emission Tomography-multiparametric MRI (PET-mpMRI), in 12 treatment-naïve and 10 stereotactic radiosurgery (SRS)-treated patients (± combination therapy within 4–8 weeks). High FPIA uptake was seen in all IMD compared to contralateral white matter, regardless of ECD tumour-of-origin (p = 0.0001) and FPIA-PET volumes extended beyond CE-MRI volumes in treatment-naïve but not SRS-treated tumours. Patients with maximum PET Standardised Uptake Value, (SUVmax) ≥ 2.0 showed particularly short overall-survival (median 4 v 15 months, p = 0.0136), while CE-MRI was uninformative regarding outcome; a PET-mpMRI grade-measure also provided non-invasive prediction of overall-survival, warranting larger studies of PET-mpMRI. Independent metabolomics analyses were consistent with shared adaptation of IMD to utilise or accumulate monocarboxylates and acylcarnitines, respectively, providing a common phenotypic basis to FPIA-PET. Reprogrammed monocarboxylate metabolism-related FPIA-PET provides new insights into annotating IMD, to be expounded in future opportunities for therapy decisions for the growing number of cancer patients with IMD [Trial registration reference: Clinicaltrials.gov NCT04807582; 3rd November 2021, retrospectively registered].