Tumor-to-blood ratio for assessment of fibroblast activation protein receptor density in pancreatic cancer using [⁶⁸Ga]Ga-FAPI-04

[⁶⁸Ga]Ga-FAPI PET/CT has been widely used in clinical diagnosis and radiopharmaceutical therapy. In this study, tumor-to-blood ratio (TBR) was evaluated as a powerful tool for semiquantitative assessment of [⁶⁸Ga]Ga-FAPI-04 tumor uptake and as an effective index for tumors with high FAP expression in theranostics.

Nine patients with pancreatic cancer underwent a 60-min dynamic PET/CT scan by total-body PET/CT (with a long AFOV of 194 cm) after injection of [⁶⁸Ga]Ga-FAPI-04. After dynamic PET/CT scan, three patients received chemotherapy and underwent the second dynamic scan to evaluate treatment response. Time-activity curves (TACs) were obtained by drawing regions of interest for primary pancreatic lesions and metastatic lesions. The lesion TACs were fitted using four compartment models by the software PMOD PKIN kinetic modeling. The preferred pharmacokinetic model for [⁶⁸Ga]Ga-FAPI-04 was evaluated based on the Akaike information criterion. The correlations between simplified methods for quantification of [⁶⁸Ga]Ga-FAPI-04 (SUVs; tumor-to-blood ratios [TBRs]) and the total distribution volume (V_t) estimates obtained from pharmacokinetic analysis were calculated.

In total, 9 primary lesions and 25 metastatic lesions were evaluated. The reversible two-tissue compartment model (2TCM) was the most appropriate model among the four compartment models. The total distribution volume V_t values derived from 2TCM varied significantly in pathological lesions and background regions. A strong positive correlation was observed between TBR_mean and V_t from the 2TCM model in pathological lesions (R²=0.92, P<0.001). The relative difference range for TBR_mean was 2.1% compared to the reduction rate of V_t in the patients who were treated with chemotherapy.

A strong positive correlation was observed between TBR_mean and V_t for [⁶⁸Ga]Ga-FAPI-04. TBR_mean reflects FAP receptor density better than SUV_mean and SUV_max, and would be the preferred measurement tool for semiquantitative assessment of [⁶⁸Ga]Ga-FAPI-04 tumor uptake and as a means for evaluating treatment response.