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Development of Integrin α5β1-targeted PET/NIR imaging probes for glioblastoma intraoperative navigation and intracavity targeted radionuclide therapy
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Researchers developed integrin α5β1-targeted peptide probes labeled with 68Ga, ICG, or 177Lu to enable preoperative PET imaging, intraoperative NIR-II fluorescence-guided resection, and post-surgical radionuclide therapy for glioblastoma, achieving significantly reduced tumor recurrence in mouse models compared to standard surgery. This multimodal theranostics work has no direct relevance to microplastic pollution research but reflects advances in targeted delivery chemistry that informs how nanoparticle and microparticle surface functionalization can be exploited for tissue-specific accumulation.
ABSTRACT Incomplete extent of tumor resection is the major factor of glioblastoma recurrence, leading to its poor prognosis. Developing therapies that enable the minimal tumor cell remnant during surgical resection is a major challenge to combat this aggressive cancer. This study develops a glioblastoma integrin α5β1-selective peptide binder through series strategy screening and labeling it with 68 Ga, indocyanine green (ICG), or 177 Lu for efficacious multimodal treatment. This strategy combines positron emission tomography (PET) imaging for preoperative diagnosis, intraoperative NIR-II fluorescence-guided surgery for maximal tumor resection, and followed by intracavity targeted radionuclide therapy for elimination of residual tumor cells. We identified GR, with five arginine mutation, exhibiting superior integrin α5β1 binding affinity and brain penetration. [ 68 Ga]GR demonstrated substantial tumor uptake and prolonged retention time in both mouse models and tissues from glioblastoma patients. The guidance of ICG-GR achieved accurately intraoperative tumor imaging and maximal tumor resection in orthotopic mouse glioblastoma models. Notably, combining intracavity administration of [ 177 Lu]GR following ICG-GR guiding resection markedly inhibited tumor growth and reduced possibility of tumor recurrence compared with surgery alone (unguided or ICG-GR–guided) or unguided surgery followed by [ 177 Lu]GR. Therefore, we have reported the integrin α5β1-targeted radionuclide and optical agents for maximal elimination of tumor cells during surgical resection in glioblastoma patients. HIGHLIGHTS GR is a glioblastoma-specific peptide with both favorable binding affinity superior brain penetration. ICG-GR is a glioblastoma-targeted NIR probe enabling maximal surgical resection. ICG-GR-guided surgery with [ 177 Lu]GR-based adjuvant therapy allows robust elimination of tumor cells.
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