RadioMedix and Vect-Horus have dosed the first patient in an exploratory IND evaluating 203Pb-RMX-VH-PIB, an LDL receptor–targeted SPECT imaging agent, in glioblastoma multiforme and pancreatic ductal adenocarcinoma. The study is designed to characterize safety, dosimetry, and biodistribution, with the tracer intended to serve as the diagnostic companion for a future targeted alpha therapy program.
The core move is a first-in-human test of a theranostic pair anchored on LDLR, with 203Pb deployed for imaging to inform potential therapeutic development with an alpha-emitting counterpart. Preclinical work suggested tumor accumulation and the ability to traverse the blood–brain barrier, a prerequisite for relevance in GBM. The trial will quantify human tumor uptake and normal tissue exposure across brain and abdominal organs to determine whether the biology is actionable and whether the dosimetry profile supports advancing to treatment studies.
Strategically, this is a platform-expansion play. Sponsors have crowded into PSMA and SSTR radioligand spaces; LDLR offers a broader solid tumor footprint and the possibility of a cross-indication program if uptake is consistent. Starting with an exploratory IND de-risks the therapeutic path by establishing patient-selection criteria and dosing windows before committing to alpha therapy development, where regulatory scrutiny around dosimetry and organ toxicity is high. Pairing a lead-203 diagnostic with the anticipated alpha therapeutic analog also signals a vertically aligned theranostic model: one isotope and chemistry backbone designed to translate imaging readouts directly into treatment decisions. RadioMedix’s in-house manufacturing capacity positions the program to manage short half-life radionuclide logistics and scale if the signal is there, while Vect-Horus contributes vector engineering aimed at receptor-mediated delivery, including across the BBB.
For sites, this is operationally feasible but not trivial. SPECT is widely available, which broadens site participation compared to PET-only programs; yet, precise, multi-timepoint imaging and radiation safety workflows will still demand nuclear medicine coordination. If the program progresses to alpha therapy, centers will need readiness for handling short-lived alpha emitters, rigorous patient-specific dosimetry, and fast-turnaround radiopharmacy—capabilities unevenly distributed outside high-volume academic hubs. CROs will need to manage time-sensitive radiopharmaceutical supply chains and protocol adherence around imaging schedules. Regulators continue to push for tighter dosimetry justification and organ risk characterization in alpha programs; clean biodistribution data in CNS and pancreatic tissues will be critical to win alignment on subsequent therapeutic trials. For sponsors and vendors, the readout will inform whether LDLR can support a biomarker-lite, receptor-expression–agnostic enrollment strategy, or whether companion diagnostics must incorporate thresholds for uptake.
What to watch next is whether human data confirm sufficient tumor-to-background ratios in both GBM and PDAC, with acceptable marrow, kidney, liver, and brain dosimetry. Evidence of reliable BBB penetration in GBM would materially differentiate the asset and open the door to a treatment IND using an alpha-emitting analog, likely with imaging-based eligibility to enrich responders. The key risks are heterogeneous LDLR expression, off-target uptake that constrains therapeutic dosing, and isotope supply chain resilience as programs transition from imaging to therapy. If early signals are positive, expect a basket-style expansion across LDLR-high solid tumors and a rapid pivot to a therapy study leveraging the same vector. If not, the program will need to refine patient selection or vector design before alpha escalation.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
