Validation of a FAP-Expressing Glioblastoma Xenograft Model for Radioligand Therapy Development

A reproducible preclinical platform demonstrating target expression, biodistribution, and dose-dependent efficacy of [¹⁷⁷Lu]Lu-FAP-2286

Glioblastoma (GBM) remains one of the most aggressive and treatment-resistant cancers, highlighting the urgent need for more targeted and effective therapeutic strategies. Radioligand therapy (RLT) has emerged as a promising approach, enabling selective delivery of radiation to tumor cells while minimizing damage to healthy tissue. Fibroblast Activation Protein (FAP), highly expressed in GBM and tumor-associated fibroblasts, represents a compelling target for this modality.

In this study, we present the validation of a U87-MG FAP-expressing glioblastoma xenograft model as a robust and reproducible platform for evaluating targeted radioligand therapies. Using [¹⁷⁷Lu]Lu-FAP-2286, we demonstrate consistent tumor growth kinetics, dose-dependent anti-tumor efficacy, and quantitative biodistribution via SPECT imaging. This model supports reliable study design and execution, enabling precise alignment with radionuclide half-life and imaging timepoints, and provides a scalable foundation for advancing FAP-targeted therapeutics and other targeted oncology modalities.

What You Will Learn

• How a validated U87-MG xenograft model enables reproducible tumor growth for reliable RLT study design
• Evidence of dose-dependent anti-tumor efficacy of [¹⁷⁷Lu]Lu-FAP-2286 in a FAP-expressing GBM model
• Insights into biodistribution and tumor retention using quantitative SPECT imaging
• Confirmation of FAP and clinically relevant marker expression through in vitro and ex vivo analysis
• How this model can be applied to support broader targeted therapy development, including RLT, ADCs, and small molecules

Learn more about Perceptive Discovery’s preclinical oncology services here.