image: Figure 1: Panel of various pediatric tumors comparing H&E staining, FRα, and FRβ protein expression within the tumor. None of these tumors demonstrate FRα expression; however all of the tumors demonstrate moderate to strong FRβ expression (brown staining). Row 1: Ewing Sarcoma in a pulmonary metastatic lesion of a 20-year-old. Row 2: Primary Synovial Sarcoma in a 17-year-old. Row 3: Osteosarcoma in a pulmonary metastatic lesion of a 15-year-old. Row 4: Primary Wilms tumor in a 7-year-old. Row 5: Primary Rhabdomyosarcoma (RMS) in a 2-year-old. H&E slides at 10x magnification. FRα and FRβ stained slides at 20x magnification.
Credit: Copyright: © 2025 Dodd et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
“This pre-clinical study demonstrates a broad potential application for pafolacianine in pediatric solid tumor resection.”
BUFFALO, NY – October 20, 2025 – A new research paper was published in Volume 16 of Oncotarget on October 16, 2025, titled “Widespread folate receptor expression in pediatric and adolescent solid tumors – opportunity for intraoperative visualization with the novel fluorescent agent pafolacianine.”
In this study, led by first author Ashley C. Dodd from Ann & Robert H. Lurie Children’s Hospital and corresponding author Timothy B. Lautz from the same institution and Northwestern University Feinberg School of Medicine, researchers discovered that folate receptor beta (FRβ) is widely expressed in various pediatric and adolescent solid tumors. This finding highlights FRβ as a promising target for improving the accuracy of tumor surgery using a fluorescent imaging agent known as pafolacianine.
Pediatric cancers are often challenging to remove completely during surgery, particularly when tumors spread or form small metastases. Fluorescence-guided surgery is a method that helps surgeons better identify tumors during operations using special imaging dyes. However, commonly used dyes such as indocyanine green are not tumor-specific and rely on general features of blood vessel permeability, limiting their precision.
In this study, researchers investigated the potential of pafolacianine, a next-generation dye that targets folate receptors, for pediatric use. Folate receptors are proteins commonly found on the surface of cancer cells. Pafolacianine is already FDA-approved for adults with ovarian and lung cancers due to its ability to bind these receptors and highlight tumors during surgery.
The research team analyzed tissue samples from 13 young patients diagnosed with various cancers, including Wilms tumor, osteosarcoma, synovial sarcoma, rhabdomyosarcoma, Ewing sarcoma, and neuroblastoma. The results showed that FRα was predominantly absent, whereas FRβ was present in 100% of the tumor samples. Notably, FRβ appeared both on the tumor cells and in the surrounding tumor microenvironment but showed little to no expression in normal tissue, making it an excellent candidate for targeted imaging.
“In this study, we performed immunohistochemistry staining on slides obtained from a range of pediatric patients with solid tumors.”
This consistent expression of FRβ in pediatric tumors is a significant and novel finding. Earlier studies primarily linked FRβ to immune cells called tumor-associated macrophages. This study reveals that FRβ is also expressed directly on tumor tissue, which could help surgeons better distinguish cancer from healthy tissue during procedures.
Based on these results, the team has launched a clinical trial to evaluate pafolacianine in children undergoing surgery for metastatic lung tumors. If successful, this method could make pediatric cancer surgery safer and more effective.
Overall, this study suggests that targeting FRβ with pafolacianine could serve as a tumor-agnostic imaging strategy, applicable across a wide range of pediatric solid tumors. This represents a potential advancement in real-time surgical imaging and a step forward in pediatric cancer care.
DOI: https://doi.org/10.18632/oncotarget.28772
Correspondence to: Timothy B. Lautz – TLautz@luriechildrens.org
Abstract video: https://www.youtube.com/watch?v=0its0QkOcwM
Keywords: cancer, folate receptor, fluorescent-guided surgery, pediatric tumors, pafolacianine, RNA sequencing
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Journal
Oncotarget
Method of Research
News article
Subject of Research
Cells
Article Title
Widespread folate receptor expression in pediatric and adolescent solid tumors - opportunity for intraoperative visualization with the novel fluorescent agent pafolacianine
Article Publication Date
16-Oct-2025
COI Statement
Authors have no conflicts of interest to declare.