(1) Background: We aimed to quantitatively investigate [68Ga]Ga-FAPI-04 uptake in normal organs and to assess a relationship with the extent of FAPI-avid
tumor burden. (2) Methods: In this single-center retrospective analysis, thirty-four patients with solid
cancers underwent a total of 40 [68Ga]Ga-FAPI-04 PET/CT scans. Mean standardized uptake values (SUVmean) for normal organs were established by placing volumes of interest (VOIs) in the heart, liver, spleen, pancreas, kidneys, and bone marrow. Total
tumor burden was determined by manual segmentation of
tumor lesions with increased uptake. For
tumor burden, quantitative assessment included maximum SUV (SUVmax),
tumor volume (TV), and fractional
tumor activity (FTA = TV × SUVmean). Associations between uptake in normal organs and
tumor burden were investigated by applying Spearman's rank correlation coefficient. (3) Results: Median SUVmean values were 2.15 in the pancreas (range, 1.05-9.91), 1.42 in the right (range, 0.57-3.06) and 1.41 in the left kidney (range, 0.73-2.97), 1.2 in the heart (range, 0.46-2.59), 0.86 in the spleen (range, 0.55-1.58), 0.65 in the liver (range, 0.31-2.11), and 0.57 in the bone marrow (range, 0.26-0.94). We observed a trend towards significance for uptake in the myocardium and
tumor-derived SUVmax (ρ = 0.29, p = 0.07) and TV (ρ = -0.30, p = 0.06). No significant correlation was achieved for any of the other organs: SUVmax (ρ ≤ 0.1, p ≥ 0.42), TV (ρ ≤ 0.11, p ≥ 0.43), and FTA (ρ ≤ 0.14, p ≥ 0.38). In a sub-analysis exclusively investigating patients with high
tumor burden, significant correlations of myocardial uptake with
tumor SUVmax (ρ = 0.44; p = 0.03) and
tumor-derived FTA with liver uptake (ρ = 0.47; p = 0.02) were recorded. (4) Conclusions: In this proof-of-concept study, quantification of [68Ga]Ga-FAPI-04 PET showed no significant correlation between normal organs and
tumor burden, except for a trend in the myocardium. Those preliminary findings may trigger future studies to determine possible implications for treatment with radioactive FAP-targeted drugs, as higher
tumor load or uptake may not lead to decreased doses in the majority of normal organs.