Potential of PSMA-targeting radioligand therapy for malignant primary and secondary brain tumours using super-selective intra-arterial administration: a single centre, open label, non-randomised prospective imaging studyResearch in context
Ilanah J. Pruis,
Pieter Jan van Doormaal,
Rutger K. Balvers,
Martin J. van den Bent,
Anita A. Harteveld,
Linda C. de Jong,
Mark W. Konijnenberg,
Marcel Segbers,
Roelf Valkema,
Frederik A. Verburg,
Marion Smits,
Sophie E.M. Veldhuijzen van Zanten
Affiliations
Ilanah J. Pruis
Department of Radiology and Nuclear Medicine, Erasmus MC, Dr. Molewaterplein 40, 3015 GD, Rotterdam, the Netherlands; Brain Tumour Centre, Erasmus MC Cancer Institute, Dr. Molewaterplein 40, 3015 GD, Rotterdam, the Netherlands
Pieter Jan van Doormaal
Department of Radiology and Nuclear Medicine, Erasmus MC, Dr. Molewaterplein 40, 3015 GD, Rotterdam, the Netherlands
Rutger K. Balvers
Brain Tumour Centre, Erasmus MC Cancer Institute, Dr. Molewaterplein 40, 3015 GD, Rotterdam, the Netherlands; Department of Neurosurgery, Erasmus MC, Dr. Molewaterplein 40, 3015 GD, Rotterdam, the Netherlands
Martin J. van den Bent
Department of Neurology, Erasmus MC Cancer Institute, Dr. Molewaterplein 40, 3015 GD, Rotterdam, the Netherlands
Anita A. Harteveld
Department of Radiology and Nuclear Medicine, Erasmus MC, Dr. Molewaterplein 40, 3015 GD, Rotterdam, the Netherlands
Linda C. de Jong
Department of Radiology and Nuclear Medicine, Erasmus MC, Dr. Molewaterplein 40, 3015 GD, Rotterdam, the Netherlands
Mark W. Konijnenberg
Department of Radiology and Nuclear Medicine, Erasmus MC, Dr. Molewaterplein 40, 3015 GD, Rotterdam, the Netherlands
Marcel Segbers
Department of Radiology and Nuclear Medicine, Erasmus MC, Dr. Molewaterplein 40, 3015 GD, Rotterdam, the Netherlands
Roelf Valkema
Department of Radiology and Nuclear Medicine, Erasmus MC, Dr. Molewaterplein 40, 3015 GD, Rotterdam, the Netherlands
Frederik A. Verburg
Department of Radiology and Nuclear Medicine, Erasmus MC, Dr. Molewaterplein 40, 3015 GD, Rotterdam, the Netherlands
Marion Smits
Department of Radiology and Nuclear Medicine, Erasmus MC, Dr. Molewaterplein 40, 3015 GD, Rotterdam, the Netherlands; Brain Tumour Centre, Erasmus MC Cancer Institute, Dr. Molewaterplein 40, 3015 GD, Rotterdam, the Netherlands; Medical Delta, Delft, Huismansingel 4, 2629 JH, Delft, the Netherlands
Sophie E.M. Veldhuijzen van Zanten
Department of Radiology and Nuclear Medicine, Erasmus MC, Dr. Molewaterplein 40, 3015 GD, Rotterdam, the Netherlands; Brain Tumour Centre, Erasmus MC Cancer Institute, Dr. Molewaterplein 40, 3015 GD, Rotterdam, the Netherlands; Corresponding author. Dr. Molewaterplein 40, 3015 GD, Rotterdam, the Netherlands.
Summary: Background: The aim of this study was to provide quantitative evidence for the potential of PSMA-targeting radioligand therapy (RLT) as treatment approach for malignant brain tumours, and to explore whether tumour uptake could be enhanced by super-selective intra-arterial (ssIA)-administration. Methods: Ten patients (n = 5 high-grade glioma, n = 5 brain metastasis) received 1.5 MBq/kg [68Ga]Ga-PSMA-11 intravenously and, within 7 days, intra-arterially (i.e., selectively in tumour-feeding arteries), followed twice by PET-MRI at 90, 165 and 240 min post-injection. Patient safety was monitored for each procedure. Standardised uptake values (SUVs) were obtained for tumour, healthy-brain, salivary glands and liver. Tumour-to-salivary-gland (T/SG) and tumour-to-liver (T/L) uptake-ratios were calculated. Findings: No adverse events requiring study termination occurred. All patients showed uptake of [68Ga]Ga-PSMA-11 at the tumour site. Uptake was a median 15-fold higher following ssIA-administration (SUVmax median: 142.8, IQR: 102.8–245.9) compared to IV-administration (10.5, IQR:7.5–13.0). According to the bootstrap analysis, mean SUVmax after ssIA (168.8, 95% CI: 110.6–227.0) was well beyond the 95% confidence-interval of IV administration (10.5, 95% CI: 8.4–12.7). Uptake in healthy-brain was negligible, independent of administration route (SUVmean <0.1–0.1). Off-target uptake was comparable, resulting in more favourable T/SG- and T/L-ratios of 8.4 (IQR: 4.4–11.5) and 26.5 (IQR: 14.0–46.4) following ssIA, versus 0.5 (IQR: 0.4–0.7) and 1.8 (IQR: 1.0–2.7) for IV-administration. Interpretation: ssIA-administration is safe and leads to a median fifteen-fold higher radioligand uptake at the tumour site, therewith qualifying more patients for treatment and enhancing the potential of therapy. These results open new avenues for the development of effective RLT-based treatment strategies for patients with brain tumours. Funding: Semmy Foundation.
