# Intra-Arterial Radioligand Therapy in Brain Cancer: Bridging Nuclear Medicine and Interventional Neuroradiology

## TL;DR

This review explores how delivering radioligand therapy directly into arteries may improve treatment for hard-to-treat brain tumors.

## Contribution

The paper highlights the novel use of intra-arterial delivery for radioligand therapy in brain cancer, showing higher uptake and dosimetric benefits.

## Key findings

- Intra-arterial RLT achieves higher radionuclide uptake in PET imaging compared to intravenous delivery.
- Dosimetric models show increased absorbed doses with minimal toxicity and uptake in healthy brain tissue.
- No significant differences in liver or salivary gland accumulation were observed between delivery routes.

## Abstract

Recurrent brain tumors—including high-grade gliomas, brain metastases, and aggressive meningiomas—continue to carry a poor prognosis, with high mortality despite therapeutic advances. The aim of this narrative review is to summarize and critically discuss the current evidence on the role of intra-arterial radioligand therapy (RLT) in the treatment of recurrent brain tumors. RLT, a targeted form of radionuclide therapy, has gained increasing attention for its potential theranostic applications in neuro-oncology. A literature search was conducted using PubMed and Scopus, including clinical studies evaluating intra-arterial radioligand delivery in central nervous system tumors. Recent research has explored intra-arterial administration of radioligands targeting somatostatin receptors and prostate-specific membrane antigen (PSMA). Somatostatin receptors are overexpressed in meningiomas, while PSMA is highly expressed in the neovasculature of glioblastomas and brain metastases; both targets can be addressed using lutetium-177 (177Lu)- or actinium-225 (225Ac)-labeled radiopharmaceuticals, traditionally delivered intravenously. Available evidence indicates that the intra-arterial route achieves markedly higher radionuclide uptake on 68Ga-PSMA-11 and 68Ga-DOTATOC PET, as well as increased absorbed doses in dosimetric models. Dosimetric analyses consistently show greater tracer accumulation compared with intravenous administration, without evidence of significant peri-procedural toxicity. Uptake in healthy brain tissue is minimal, and no relevant differences have been reported in liver or salivary gland accumulation between intra-arterial and intravenous RLT. Although based on heterogeneous and limited data, intra-arterial RLT appears to be a promising therapeutic strategy for recurrent brain tumors. Future research should focus on improving radioligand delivery beyond the blood–brain barrier and enhancing effective tumor targeting.