Proliferation PET Image to Characterize Pathological Spatial Features in Patients With Non-Small Cell Lung Cancer: A Pilot Study

Purpose: 18F-FLT-PET imaging was proposed as a tool for measuring in vivo tumor cell proliferation and detecting sub-volumes to propose escalation in radiotherapy. The aim of this study was to validate whether high FLT uptake areas in 18F-FLT PET/CT are coincident with tumor cell proliferation distribution indicated by Ki-67 staining in non-small cell lung cancer, thus provide theoretical support for the application of dose painting guided by 18F-FLT PET/CT. Materials and methods: Twelve treatment naive patients with biopsy proven NSCLC underwent 18F-FLT PET/CT scans followed by lobectomy were enrolled. The surgical specimen was dissected into 4-7 μm sections at approximately 4-mm intervals. The best slice was sort out to complete Ki-67 staining. Maximum Ki-67 labelling Index and SUVmax of the corresponding PET image was calculated. The correlation between Ki-67 Labelling Index and SUVmax of FLT was determined using Spearman Correlation analysis. High uptake areas and high proliferating areas were delineated on the two images, respectively, and their location was compared. Results: The maximal SUV was 3.26 ± 0.97 (1.96-5.05), maximal Ki-67 labeling index was 49% ± 27.56% (5%-90%). Statistical analysis didn’t reveal a significant correlation between them (r = -0.157, P = 0.627, > 0.05). 9 patients can contour high proliferating area on Ki-67 staining slice, and eight can contour the high uptake areas. In 4 patients, we can observe a generally close distribution of high uptake areas and high proliferating areas, in one patient, both the uptake level and proliferation status was low, while the others didn’t not find a significant co-localization. Conclusion: Noninvasive 18F-FLT PET assessing the proliferative status may be a valuable aid to guide dose painting in NSCLC, but it needs to be confirmed further.