Advantages of FBPA PET in evaluating early response of anti PD-1 immunotherapy in tumor-bearing mice: comparison to FDG PET

Introduction: PET with L-4-borono-2-F-18 fluoro-phenylalanine (FBPA) was reported to be useful to differentiate malignant tumors and inflammation. Although immunotherapy with immune checkpoint inhibitors (ICIs) has increasingly been applied to cancer treatment recently, FDG PET may not be suitable to determine the effect of ICIs because of false-positive findings caused by treatment-related inflammation. In this study, we aimed to demonstrate that FBPA PET allowed detection of the early response of anti PD-1 immunotherapy in tumor-bearing mice, comparing the results with those of FDG PET.

Methods: Mice inoculated B16F10 melanoma cells were prepared. Anti-mouse PD-1 antibody or PBS was administered twice i.p. to the tumor-bearing mice on Day 0 (3 days after inoculation) and Day 5 (treatment or control group <trg cog="" or="">). Tumors were measured using calipers, and the volume was calculated. </trg>PET/CT imaging was performed twice for each mouse on Day 0 before the anti PD-1 antibody/PBS administration and on Day 7 using a micro-PET/CT scanner. FBPA and FDG PET/CT studies were conducted separately (n=5 each for FBPA TrG, FBPA CoG, FDG TrG, and FDG CoG). SUVmax and the tumor to liver ratio (T/L ratio) were used as parameters exhibiting tumor activity. Tumor uptake volume (TUV) and metabolic tumor volume (MTV) were also calculated for FBPA and FDG, respectively. Changes between pre- and posttreatment tumor activity were observed using the formula as follows: [(posttreatment parameter values/pretreatment values - 1) × 100] (%).

Results: Tumors in TrG were smaller than those in CoG on Day 7 (489 vs 918 mm3, p < 0.01). SUVmax and T/L ratio represented no differences between TrG and CoG in both FBPA and FDG PET before treatment. Posttreatment FBPA PET demonstrated that SUVmax, T/L ratio, and TUV in TrG were statistically smaller than those in CoG. %T/L ratio and %SUVmax exhibited the same trend in FBPA PET. However, posttreatment FDG PET revealed no differences in all parameters between TrG and CoG. T/L ratio and %SUVmax in TrG represented larger values than those in CoG without statistical significances in this setting. Details are shown in Table.

Conclusions: This study demonstrated that FBPA PET allowed detection of the early response of anti PD-1 immunotherapy in tumor-bearing mice. FDG PET did not detect the response. Further studies are required to determine whether FBPA PET is useful in evaluating treatment effect of ICIs in humans.