Feasibility of [18F]fluoropivalate hybrid PET/MRI for imaging lower and higher grade glioma: a prospective first-in-patient pilot study

Abstract

Purpose: MRI and PET are used in neuro-oncology for the detection and characterisation of lesions for malignancy to target surgical biopsy and to plan surgical resections or stereotactic radiosurgery. The critical role of short-chain fatty acids (SCFAs) in brain tumour biology has come to the forefront. The non-metabolised SCFA radiotracer, [¹⁸F]fluoropivalate (FPIA), shows low background signal in most tissues except eliminating organs and has appropriate human dosimetry. Tumour uptake of the radiotracer is, however, unknown. We investigated the uptake characteristics of FPIA in this pilot PET/MRI study.

Methods: Ten adult glioma subjects were identified based on radiological features using standard-of-care MRI prior to any surgical intervention, with subsequent histopathological confirmation of glioma subtype and grade (lower-grade - LGG - and higher-grade - HGG - patients). FPIA was injected as an intravenous bolus injection (range 342-368 MBq), and dynamic PET and MRI data were acquired simultaneously over 66 min.

Results: All patients tolerated the PET/MRI protocol. Three patients were reclassified following resection and histology. Tumour maximum standardised uptake value (SUV_max,60) increased in the order LGG (WHO grade 2) < HGG (WHO grade 3) < HGG (WHO grade 4). The net irreversible solute transfer, Ki, and influx rate constant, K1, were significantly higher in HGG (p < 0.05). Of the MRI variables studied, DCE-MRI-derived extravascular-and-extracellular volume fraction (v_e) was high in tumours of WHO grade 4 compared with other grades (p < 0.05). SLC25A20 protein expression was higher in HGG compared with LGG.

Conclusion: Tumoural FPIA PET uptake is higher in HGG compared to LGG. This study supports further investigation of FPIA PET/MRI for brain tumour imaging in a larger patient population.

Clinical trial registration: Clinicaltrials.gov, NCT04097535.

Keywords: FPIA; Glioma; PET/MRI; Short-chain fatty acid; [18F]fluoropivalate.

Fig. 1

FPIA PET/MRI images in patients with grades II, III and IV gliomas. Axial PET and MRI images for grade II (PT01 and PT11), grade III (PT03, PT05, PT07) and grade IV (PT02, PT04, PT08, PT09, PT10) glioma patients including standardised uptake value for the last 5 time frames (SUV) from FPIA PET, T1 weighted MRI sequence, dynamic contrast-enhanced MRI (DCE)-contrast agent plasma/interstitium transfer rate constant (Ktrans), dynamic susceptibility contrast (DSC) MRI-cerebral blood volume (CBV), arterial spin labelling MRI-cerebral blood flow (CBF) and diffusion-weighted imaging MRI-apparent diffusion coefficient (ADC)

Fig. 2

Image congruence. (A) Lesion mask outlined on the post-contrast T1 MRI image (red) and on the SUV₄₀ and SUV₃₀ (green). (B) Dynamic contrast-enhanced (DCE) MRI and SUV average tissue time activity curves in grade II (blue), grade III (red) and grade IV (green) for lesion or CWM

Fig. 3

Blood to brain and tumour transit of FPIA. (A) Comparison of structural (longitudinal relaxation time on MRI-T1 post-contrast) and functional (FPIA PET SUVc) image sets from grade II (PT11), grade III (PT02) and grade IV (PT07) patients. (B) Spectrum of kinetic components evaluated in the lesion and CWM by spectral analysis. (C) Boxplots showing K1, Ki and V_T parameters in grades II, III, IV and CWM

Fig. 4

Assessment of the objective combination of PET and MRI variables for grade prediction. The least absolute shrinkage and selection operator (LASSO) was applied to extract a composite vector for tumour grade prediction from 24 (dynamic included) or 20 (static only) parameters determined by analysis of simultaneously acquired PET and MRI data. Five-fold cross-validation was performed to select lambda minimum to give the minimum cross-validated error for classifying LGG (grade II) versus HGG (grades III and IV) when (A) the PET variables were restricted to static data or (B) included dynamic PET data. The feature coefficients (b value) are indicated. (C) Boxplots showing v_e parameter in grades II, III, IV and CWM