Quantitative Assessment of Cerebrovascular Malformation using¹⁸F-GE180 PET/MRI

Introduction: Neuroinflammation plays a key role in both the pathogenesis and the progression of cerebral cavernous malformations (CCM) and brain arteriovenous malformations (BAVM). [¹⁸F]GE-180 is a translocator protein (TSPO) targeting PET tracer, developed for neuroinflammation imaging. The objective of this study was to describe characteristics of [¹⁸F]GE-180 uptake in the brains of patients with CCM and to investigate whether a functional polymorphism in the TSPO p.Thr147Ala is effective for [¹⁸F]GE-180 PET screening.

Methods: Six patients (five CCM and one BAVM) with an average age 50 (five males and one female), were enrolled and scanned on a GE PET/MR system. Genotyping of TSPO Ala147Thr polymorphism was performed to classify subjects as either high affinity binders (HAB) or mixed affinity binders (MAB); low affinity binders (LAB) were excluded. Subjects underwent a 60 or 90 min PET/MR scan after the administration of 8.2±1.9 mCi [¹⁸F]GE-180. For quantification of the radiotracer uptake, standardized uptake value (SUV), a validated method for this radiotracer was used. In addition, standardized uptake value ratio (SUVr) calculations were made using striatum as a reference. In order to derive SUVs consistently between all patients, all brain PET images were summed over 50-60 min when the total scan duration was 60 minutes or 60-90 min when the total scan duration was 90 minutes, and were normalized to an AAL-ROI template to derive SUVs in defined brain regions using PMOD (version 3.3). For the lesion specific SUVs, quantitative susceptibility maps (QSM), that were acquired simultaneously with the PET data, were used to define the location of the vascular malformation.

Results: Patients were classified as HAB (n=5) or MAB (n=1) based on genotype. Low [¹⁸F]GE-180 uptake was seen globally in non-lesion brain tissue ROIs, and lesion-specific uptake was visible as seen in Fig. 1. The temporal pole and cuneus showed high radiotracer uptake, the paracentral lobule and hippocampus showed moderate uptake, and striatum had the lowest uptake, with average SUVs of 0.63, 0.59, 0.55, 0.53 and 0.32, respectively. The regional SUVr was 1.95,1.82, 1.68 and 1.64, respectively. The size of lesions ranged between 3.2 mm³ and 3.8 cm³. Average CCM SUV (g/ml) and SUVr were 0.55±0.22 and 1.51±0.52, respectively.

Conclusions: The distribution characteristics of [¹⁸F]GE-180 in the brain has demonstrated the potential of this tracer as a marker of neuroinflammation that may be relevant for tracking CCM disease progression and evaluating the effectiveness of potential drug therapies in future clinical trials.