Translocator protein (TSPO) positron emission tomography imaging and expression in patients with brain metastases

18 kDa translocator protein (TSPO) is a biomarker for inflammatory conditions. However, full kinetic positron emission tomography (PET) modeling has rarely been used to quantify brain tumors, and it has never been used in brain metastases (BMs). This proof-of-principle study quantified TSPO expression using full kinetic modeling in patients with BMs from various types of peripheral primary tumors.

Nine adult patients with BMs and 12 healthy volunteers (HVs) took part in the study. The total distribution volume (V_T) of ¹¹C-ER176 was calculated with a two-tissue compartment model (2TCM) and metabolite-corrected arterial input function in the BMs and in the rest of the brain. Immunohistochemistry (IHC) and single-cell RNAseq database were used to quantify TSPO expression in vitro. The V_T values of the hemisphere contralateral to the BMs were compared to the cortical values of HVs.

¹¹C-ER176 uptake was increased in BMs compared with the rest of the brain of each participant. The BM time-activity curves were well-fitted by the 2TCM, and the resulting V_T (range 3.2-13 mL/cm³) was identified with precision (standard error generally < 5%). The rate constant mostly affected by the integrity of the blood-brain barrier (BBB) (K₁) was similar between the BMs and the contralateral hemisphere. TSPO expression was detected by IHC in tumor regions and variably in microglia/macrophages, a finding largely corroborated by single-cell RNAseq database. The average V_T of the rest of the brain in BM patients was significantly lower than in HVs, which may have been due to immunosuppressive therapy.

In this pilot study, full kinetic modeling quantified TSPO expression in BMs with good fit and precision. The kinetic modeling outcome parameters and the TSPO expression levels in vitro suggest that ¹¹C-ER176 binding was largely specific and not significantly affected by disruption of the BBB.