Dual-Tracer Assessment of Dynamic Changes in Reoxygenation and Proliferation Decrease During Fractionated...

Area of Science:

• Oncology
• Radiotherapy
• Medical Imaging

Background:

• Fractionated radiotherapy (FRT) is a standard cancer treatment.
• Tumor hypoxia and proliferation are key factors influencing treatment response.
• Non-invasive monitoring of these factors is crucial for optimizing radiotherapy.

Purpose of the Study:

• To assess tumor reoxygenation and inhibition during FRT using PET/CT.
• To evaluate the efficacy of 18F-fluoromisonidazole (18F-FMISO) and 18F-fluorothymidine (18F-FLT) PET/CT in monitoring these changes.
• To correlate PET/CT findings with immunohistochemical biomarkers.

Main Methods:

• A nude mouse xenograft model of head and neck squamous carcinoma (FaDu) was used.
• Fractionated radiotherapy (FRT) was administered.
• 18F-FMISO and 18F-FLT micro PET/CT imaging was performed before, during, and after FRT.
• Analysis included SUVmax, TNR, hypoxic volume (HV), and proliferative tumor volume (PTV).
• Immunohistochemistry for HIF-1α, CAIX, Ki67, and PCNA was performed.

Main Results:

• 18F-FMISO PET/CT showed significant reductions in SUVmax, TNR, and HV from pre- to inter-treatment.
• 18F-FLT PET/CT revealed a decreased PTV reduction rate from pre- to inter-treatment compared to inter- to post-treatment.
• Tumor biomarkers (HIF-1α, CAIX, Ki67, PCNA) were continuously downregulated.
• TNR (FMISO) correlated significantly with hypoxia markers, while SUVmax (FLT) correlated with proliferation markers.

Conclusions:

• Tumor reoxygenation occurs early in FRT, while proliferation inhibition is gradual.
• 18F-FMISO and 18F-FLT PET/CT are sensitive, non-invasive tools for monitoring tumor response during radiotherapy.