CTNI-76. UNLOCKING THE POWER OF LDL- RECEPTORS IN GLIOBLASTOMA

Abstract BACKGROUND Low-density lipoprotein receptors (LDLR) are overexpressed in a variety of solid tumors, including glioblastoma (GBM), and are known to play a key role in tumor proliferation and metabolic regulation.-LDLRs are also expressed on the blood-brain barrier (BBB), offering a unique gateway for receptor-mediated delivery of radiopharmaceuticals to intracranial tumors. In this study, we present initial data from eIND on the use of a novel LDLR-targeted imaging agent, ⁶⁸Ga-RMX-VH, in patients with newly diagnosed or recurrent GBM, We will also discuss the selection of the second-generation RMX_VH_PKM, which features modified blood circulation times and improved tumor-targeting properties. METHODS We initiated an open-label, single-dose, eIND-study (#155880) using 68Ga-RMX-VH PET/CT in newly diagnosed or recurrent patients with GBM. The primary objective was to assess the biodistribution and dosimetry of 68Ga-RMX-VH. The secondary objective was to correlate the extent of GBM visualized by contrast-enhanced MRI of the brain with the distribution of 68Ga-RMX-VH PET/CT in the brain, in each subject. A total of 10 GBM subjects have been scheduled for enrollment, with 5 of them enrolled in the dosimetry group. RESULTS We enrolled four patients with glioblastoma (GBM) (3 males, 1 female, aged 58–68 years) who had undergone craniotomy, adjuvant chemotherapy, and/or radiation therapy (XRT) and exhibited disease progression on MRI/CT scans. Pathological evaluation confirmed GBM with MGMT promoter methylation, IDH wild-type status, and EGFR mutation (Ki-67 = 25–60%). PET/CT imaging with ⁶⁸Ga-RMX-VH demonstrated effective targeting of the solid portion of the residual tumor, correlating well with contrast-enhanced regions on MRI or FLAIR. Activity was primarily cleared via the kidneys. These results stimulated our work on the selection of the second-generation RMX-VH-PKM, which has a longer blood circulation time and improved tumor–specific retention, as confirmed in vivo studies. CONCLUSIONS RMX-VH agents effectively target LDLR-overexpressing glioblastoma (GBM), with ⁶⁸Ga- or 203Pb-labeled radiotracer uptake closely aligning with enhanced and FLAIR regions on brain MRI.