284P Clinical validation of CCR2-targeted SPECT imaging as a biomarker for monocyte-macrophage infiltration and prognosis in non-small cell lung cancer

Background: Accurate target volume delineation in radiotherapy in non-small cell (NSCLC) and small cell lung cancer (SCLC) is based on integration of CT and 18 Ffluorodeoxyglucose (18 FFDG) PET. PET imaging with fibroblast activation protein inhibitor (FAPI) enables visualization of FAP. This study evaluated 18 FFDG-vs. 18 FFAPI-74 PET/CT for target volume delineation. Methods: 40 patients with histologically confirmed advanced/recurrent lung cancer underwent both 18 FFDG and 18 FFAPI-74 PET/CT before radiotherapy. Tumor uptake was quantified using tumor-to-background ratios (tumor SUVmax / SUVmean of mediastinal blood pool). After excluding PET-negative cases, 33 datasets were analyzed. CT-based gross tumor volumes (GTVCT) were compared with semiautomatically segmented PET-derived GTVs using absolute background-based thresholds (SUV 1. 5-, 2. -, 2. 5-, or 3-fold blood pool SUVmean). Thoracic metabolic tumor volumes (MTVₜhoracic) and FAPI-avid tumor volume (FTVₜhoracic) were assessed using relative, per-lesion thresholds, i. e. , 42% isocontour of the local lesion SUVmax. Data are reported as median (1 st -3 rd quartile; Wilcoxon signed-rank test with Holm correction). Results: Median tumor-to-background ratio was higher for 18 FFAPI-74 than for 18 FFDG-PET/CT (4 2. 6-5. 1vs 3. 8 2. 6-7. 4, p = 0. 8). Median GTVCT was 94. 3 cm 3 (36. 8-177. 8). With a threshold of 1. 5, median FDG-and FAPI-derived GTVs were 28 cm 3 (10. 7-90. 4) and 31. 3 cm 3 (18-75). At thresholds of 2. 0, 2. 5, and 3. 0, median FDG-derived GTVs were 22 cm 3 (4. 3-61. 5), 11. 3 cm 3 (1. 5-43), and 6. 7 cm 3 (0. 2-37. 4, vs. 15 cm 3 (5. 6-48), 9 cm 3 (1. 6-31), and 3. 4 cm 3 (0. 4-14) for FAPI, respectively. FDGand FAPI-derived GTVs did not differ at any threshold (Holm-adjusted p 0. 05). All PET-derived GTVs were significantly smaller than GTVCT (p < 0. 001), including in patients who did not undergo prior systemic therapy. Median MTVₜhoracic and FTVₜhoracic were 19. 2 cm 3 (10-45) and 18. 8 cm 3 (11-33. 7) ;p = 0. 2. Conclusions: 18 F-FAPI-74-PET/CT shows favorable tumor-to-background uptake in lung cancer. PET-derived semiautomatically delineated GTVs differ substantially from CT-based GTVs, irrespective of use of prior systemic therapy.