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

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].