Y. Venel

Molecular Imaging of Microglial Activation in Amyotrophic Lateral Sclerosis

There is growing evidence of activated microglia and inflammatory processes in the cerebral cortex in amyotrophic lateral sclerosis (ALS). Activated microglia is characterized by increased expression of the 18 kDa translocator protein (TSPO) in the brain and may be a useful biomarker of inflammation. In this study, we evaluated neuroinflammation in ALS patients using a radioligand of TSPO, 18F-DPA-714. Ten patients with probable or definite ALS (all right-handed, without dementia, and untreated by riluzole or other medication that might bias the binding on the TSPO), were enrolled prospectively and eight healthy controls matched for age underwent a PET study. Comparison of the distribution volume ratios between both groups were performed using a Mann-Whitney’s test. Significant increase of distribution of volume ratios values corresponding to microglial activation was found in the ALS sample in primary motor, supplementary motor and temporal cortex (p = 0.009, p = 0.001 and p = 0.004, respectively). These results suggested that the cortical uptake of 18F-DPA-714 was increased in ALS patients during the “time of diagnosis” phase of the disease. This finding might improve our understanding of the pathophysiology of ALS and might be a surrogate marker of efficacy of treatment on microglial activation.

Initial evaluation in healthy humans of [18F]DPA-714, a potential PET biomarker for neuroinflammation

INTRODUCTION The translocator protein 18 kDa (TSPO), although minimally expressed in healthy brain, is up-regulated in pathological conditions, coinciding with microglial activation. It is thereby a suitable in vivo biomarker of neuroinflammation for detection, evaluation and therapeutic monitoring of brain diseases. We aimed to estimate the radiation dosimetry of the positron emission tomography (PET) TSPO radioligand [(18)F]DPA-714, and we evaluated in healthy volunteers its whole-body uptake and cerebral kinetics. METHODS Biodistribution data from mice were used for the prediction of radiation dosimetry. In human studies, a 90-min dynamic PET scan was performed in seven healthy volunteers after injection of [(18)F]DPA-714 (245±45 MBq). Arterial and venous samples were collected from two subjects, and two additional subjects were submitted to whole-body acquisition. Regions of interest were defined over cerebral structures to obtain mean time-activity curves and to estimate the distribution volume ratios by Logan graphical analysis, and over peripheral organs to obtain standard uptake values. RESULTS The effective dose estimated from biodistribution in mice was 17.2 μSv/MBq. Modeling of regional brain and plasma data showed good in vivo stability of [(18)F]DPA-714 in humans, with only 20% of blood metabolites 20 min postinjection (p.i.). Maximum cerebral uptake was observed 5 min p.i., followed by two decreasing phases: a rapid washout (5-30 min) followed by a slower phase for the remainder of PET acquisition. Whole-body images demonstrate high activity in the gallbladder, heart, spleen and kidneys. CONCLUSIONS This initial study in humans shows that [(18)F]DPA-714 is a promising PET radioligand with excellent in vivo stability and biodistribution, and acceptable effective dose estimation. Therefore, [(18)F]DPA-714 could provide a sensitive measure of neuroinflammatory changes in subsequent clinical investigations.

18F-FDG PET in Liver Transplantation Setting of Hepatocellular Carcinoma: Predicting Histology?

Purpose The aim of this study was to evaluate the prognostic value of 18F-FDG PET/CT by predicting histopathological findings in the pretransplant evaluation of patients with hepatocellular carcinoma (HCC). Patients and Methods 18F-FDG PET/CT findings of 34 patients with HCC who underwent liver transplantation were reviewed retrospectively. Visual and quantitative analysis (tumor standardized uptake values normalized to the background activity of the liver: SUVmax T/L) was done. PET tumor characteristics were compared with the histological analysis (differentiation and microvascular invasion). All patients were followed up (mean, 12 months). Results Ten patients showed tumoral uptake greater than background activity (PET+). Higher-grade tumor was more common in the 18F-FDG–avid tumor group (P < 0.05). PET+ also showed more microvascular invasion at explant pathology (P < 0.05). Only 1 patient PET+ developed HCC early recurrence (4 months) with an SUVmax T/L of 1.64. Conclusions 18F-FDG uptake is predictive for microvascular invasion and tumor differentiation. This examination has a prognostic value regarding tumor recurrence after liver transplantation for HCC.