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 3’-deoxy-3’-18F-fluorothymidine(18F-FLT) positron emission tomography /computed tomography(PET/CT) are coincident with tumor cell proliferation distribution indicated by ki-67 staining in non-small cell lung cancer(NSCLC), thus provide theoretical support for the application of dose painting and biological intensity modulated radiation therapy(BIMRT) 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 4-7um sections at approximately 4-mm intervals and stained with hematoxylin and eosin(HE). The best slice was sort out to complete ki-67 staining. SUVmax and the maximum Ki-67 labelling Index(Ki-67 LI) was calculated. High uptake areas and high proliferating areas were delineated on PET/CT and pathological images, respectively, and their location was compared. Results: In all cases it was feasible to slice and scan the tumor. The mean maximal SUV was 3.26±0.97(range, 1.96-5.05), mean maximal ki-67 labeling index was 49% ± 27.56%(5%- 90%). There was no significant correlation between SUVmax and Ki-67 maximal libeling index(r=-0.157, p=0.627, >0.05). A total of 9 patients can contour the high proliferating area on ki-67 staining slice, and eight patients can contour the high uptake areas. In 3 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, in two patients, the uptake status and proliferation status was opposite, 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 and BIMRT in NSCLC, but it needs to be confirmed further.