This study is the first systematic evaluation of folate receptor β (FRβ) expression in pediatric solid tumors, revealing its high expression in most tumor samples while normal tissues show low expression. This highlights FRβ as a potential target for intraoperative fluorescence-guided surgery. Pafolacianine, an FR-targeted near-infrared fluorescent probe already approved for adult tumors, demonstrates potential application in pediatric oncology.
Literature Overview
The article 'Widespread Expression of Folate Receptors in Pediatric and Adolescent Solid Tumors: Opportunities for Intraoperative Visualization with the Novel Fluorescent Agent Pafolacianine' published in Oncotarget reviews and summarizes FRα and FRβ expression patterns in pediatric tumor tissues. Using immunohistochemistry and RNA sequencing analysis, the study identifies widespread FRβ expression across multiple pediatric solid tumors, while FRα shows weaker expression, suggesting its potential value in intraoperative fluorescence-guided surgery.
Background Knowledge
Folate receptors are transmembrane proteins highly expressed on various tumor cell surfaces. Pafolacianine, a folate analog, specifically binds to FRα and FRβ, emitting fluorescence under near-infrared excitation for intraoperative tumor visualization. While this technology has received FDA approval for adult ovarian and lung cancers, its expression profile in pediatric tumors remains unclear. Pediatric solid tumor surgeries often face challenges including indistinct tumor margins, positive resection margins, and normal tissue damage, making real-time intraoperative imaging critically valuable. This study provides the first systematic assessment of FR expression in pediatric tumors, offering theoretical support for Pafolacianine's clinical application in pediatric oncology.
Research Methods and Experiments
This study evaluated FRα and FRβ protein expression in 19 solid tumor samples from 13 pediatric and adolescent patients using immunohistochemistry (IHC). Samples included primary and metastatic tumors across osteosarcoma, synovial sarcoma, Ewing sarcoma, rhabdomyosarcoma, Wilms tumor, DSRCT, and neuroblastoma. Publicly available RNA sequencing data were integrated to analyze gene expression levels of FRα and FRβ in pediatric tumors.
Key Conclusions and Perspectives
Research Significance and Prospects
This study provides novel target support for intraoperative fluorescence-guided surgery in pediatric solid tumors. The widespread FRβ expression suggests its potential as a universal target for intraoperative localization across multiple pediatric tumor types. A clinical trial (NCT06235125) is currently evaluating Pafolacianine's safety and feasibility in pediatric pulmonary metastases. Future research should expand sample sizes and investigate correlations between FR expression levels and clinical outcomes.
Conclusion
This systematic assessment of folate receptor expression in pediatric solid tumors reveals high FRβ expression in most tumor samples versus limited FRα expression. This establishes a theoretical basis for applying Pafolacianine, a novel fluorescence targeting agent, in pediatric tumor surgeries. Given its successful application in adults, this study supports clinical translation of Pafolacianine for intraoperative guidance in pediatric oncology. Future studies should validate its safety and efficacy in pediatric solid tumors while exploring its role in identifying micrometastases and protecting normal tissues during surgery.
