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 F]fluorodeoxyglucose ([ 18 F]FDG) PET.PET imaging with fibroblast activation protein inhibitor (FAPI) enables visualization of FAP.This study evaluated [ 18 F]FDG-vs.[ 18 F]FAPI-74 PET/CT for target volume delineation.Methods: 40 patients with histologically confirmed advanced/recurrent lung cancer underwent both [ 18 F]FDG and [ 18 F]FAPI-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 (GTV_CT) 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 (MTV_thoracic) and FAPI-avid tumor volume (FTV_thoracic) 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 F]FAPI-74 than for [ 18 F]FDG-PET/CT (4 [2.6-5.1]vs 3.8 [2.6-7.4],p = 0.8).Median GTV_CT 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 GTV_CT (p < 0.001), including in patients who did not undergo prior systemic therapy.Median MTV_thoracic and FTV_thoracic 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.