18F-AlF-FAPI nanotracer visualized the quick response of sarcoma to radiotherapy by PET/CT

Abstract

Abstract Background MRI or CT-based RECIST is the current clinical standard for evaluating the efficacy of radiation therapy. Typically, several months are required after treatment to determine the extent of tumor control, with the possibility of malignant progression. In this study, we synthesize a novel nanoscale 18F-AlF-labeled FAPI radiotracer and assess its capacity to monitor instant radiotherapy response by PET/CT in tumor xenografted mouse models and a patient with sarcoma, utilizing 18F-FDG, 68Ga-FAPI PET/CT imaging, and MRI imaging as controls. Results Current research has generated an 18F-AlF-FAPI radiotracer with an unique pharmacological architecture. The radiotracer 18F-AlF-FAPI was a colloid with a diameter of 100–200 nm. The diameter of AlF clusters ranges between 10 and 80 nm, and the majority of 18F-AlF-FAPI molecules comprise between 2 and 5 AlF clusters. In comparison to 68Ga-FAPI, 18F-AlF-FAPI has a distinct excretion mechanism and a significantly smaller background signal, resulting in a higher tumor-to-background ratio (TBR). After a single dose of 10 Gy of non-lethal X-ray therapy, the xenografted tumor in the mouse exhibited a high uptake of 18F-AlF-FAPI, followed by tumor progression. In a patient with sarcoma who underwent complete carbon ion radiotherapy (CIRT) treatment and tumor regression, tumor uptake of 18F-AlF-FAPI was barely detectable, highlighting the potential of 18F-AlF-FAPI probe-based PET/CT for visualization of quick response to CIRT radiotherapy within one month. Additionally, the tumor site in this case was around 1,4 times larger in 18F-AlF-FAPI PET imaging than in MRI and 18F-FDG PET/CT imaging. The physician finally expanded the target volume delineation for CIRT treatment based on the positive region and heterogeneity, indicating the potential of 18F-AlF-FAPI nanotracer in target volume delineation. Conclusions In PET/CT imaging, the novel 18F-AlF-FAPI nanotracer had a higher TBR and a lower background than 68Ga-FAPI due to its distinct formation. 18F-AlF-FAPI uptake was found to be favorably linked with tumor progression in tumor-xenografted mice and sarcoma patients. Compared to 18F-FDG, 68Ga-FAPI PET/CT imaging, and MRI imaging, 18F-AlF-FAPI PET/CT imaging revealed greater potential for identifying the rapid response of sarcoma to radiotherapy within one month. 18F-AlF-FAPI PET/CT imaging has also shown potential in radiotherapy target volume delineation.