P11.68.A INTRA-ARTERIAL ADMINISTRATION OF [68GA]GA-PSMA-11 IN MALIGNANT PRIMARY AND SECONDARY BRAIN TUMOURS; A NOVEL APPROACH THAT SIGNIFICANTLY INCREASES TUMOUR UPTAKE AND POTENTIAL OF/FOR THERANOSTIC STRATEGIES

Abstract

Abstract BACKGROUND Primary and secondary brain tumours carry a dismal prognosis and require new treatment strategies. First studies into novel radionuclide therapies have thus far yielded little success, potentially because of limitary uptake in tumour upon intravenous (IV) administration. The aim of the present study was to show that intra-arterial (IA) administration of radiopharmaceuticals will lead to much higher uptake and, consequently, to higher delivered dose to the tumour, which convincingly outweighs the systemic non-target uptake. MATERIAL AND METHODS Ten patients with malignant brain tumours (n=5 high-grade glioma (HGG), n=5 brain metastasis (BM)) twice received 1.5 MBq/kg [68Ga]Ga-PSMA-11 followed by PET-MRI at 90, 165 and 240 minutes post-administration, first upon IV and subsequently upon selective IA administration, with a median interval time of 5 days. Standardised uptake values (SUVs) were calculated for tumour, and non-target sites (contralateral healthy brain, salivary glands and liver) using volumes of interest (VOIs). Tumour-to-liver (T/L), tumour-to-salivary gland (T/SG) uptake-ratios and simulated achievable tumour doses with either [177Lu]Lu- or [225Ac]Ac-PSMA were calculated for each patient. Paired T-test and Wilcoxon signed rank-test were performed to compare outcomes. RESULTS All patients showed significantly higher uptake in tumour following IA administration compared to IV administration, with a median SUVmax of 142.8 (range: 31.3-336.8) versus 10.5 (range: 5.1-17.1, P=0.005). Healthy brain showed no significant uptake, independent of the route of administration (SUVmean range: <0.1-0.1). Uptake at non-target sites was comparable following IA and IV administration, resulting in more favourable T/SG-ratios of 8.4 (median, range: 1.8-18.9) for IA versus 1.8 (0.9-7.0) for IV; P=0.005 and T/L-ratios of 26.5 (7.4-68.7) for IA versus 1.8 (0.9-7.0) for IV; P=0.005. Simulations showed a maximum delivered dose to the tumours for a single treatment cycle to be 68 Gy (median, range: 5-282) for [177Lu]Lu- and 78 Gy (5-174) for [225Ac]Ac-PSMA when administered intra-arterially, versus 10 Gy (1-37) and 18 Gy (1-49), when administered intra-venously. CONCLUSION Selective IA administration of radiopharmaceuticals in malignant brain tumours leads to a significant and therapeutically relevant increase in target to non-target uptake ratios. This observation opens new avenues for the development of theranostic strategies for patients with HGG and BM whom we, to date, have no curative treatment to offer.