Preliminary evaluation of shaken baby syndrome using [¹⁸F]GE180

Objectives: Abusive head trauma (AHT) is the leading cause of death from trauma in infants and young children aged < 2 years. Shaking of the young infant with or without impact trauma is considered as one of the mechanisms of AHT. In the United States, 13-36% of AHT victims die as a result of their injuries, and 62%-96% of survivors suffer permanent physical, neurological and mental disabilities. Traditionally, computed tomography (CT) and magnetic resonance imaging (MRI) have been the most commonly used technologies to identify intracranial bleeds, parenchymal abnormalities, and skull fractures. However, AHT cases often do not show any observable defect on CT or MRI. Also, there is underestimation of severity of parenchymal abnormalities on anatomical imaging. Moreover, long-term neurological and behavioral problems, such as headache, depression, anxiety, and light sensitivity, cannot be sensitively predicted with CT or MRI. Here we propose using an 18 kDa translocator protein (TSPO) specific radiotracer [¹⁸F]GE180 for neuroinflammation and associated glial cell activation, to evaluate intracranial injury from controlled shaking in an animal model. Methods: [¹⁸F]GE180 was produced by a one-step S_N2 nucleophilic substitution reaction with the mesylate precursor (100 ^oC, 10 min) in an automatic synthesizer. 10- or 11-day old SD rat pups were shaken for 60 s at 250 rpm in a gyrating shaker and allowed to rest for 60 s. This procedure was repeated five times a day each on three consecutive days (days 1-3). The rat pups of the control group were placed in the chamber without shaking. On days 5, 8, 11, 15 after initial shaking, the rat pups were injected with [¹⁸F]GE180 (0.9-1.9 MBq in 10% ethanol in USP normal saline) and biodistribution studies at 30 min post-injection were conducted. Tissues and organs were harvested and assayed in the PerkinElmer 2480 gamma counter. The results were analyzed and then expressed as a percentage of the injected dose per gram of tissue (%ID/g). Results: [¹⁸F]GE180 was radiosynthesized in a decay corrected yield of around 35% with a radiochemical purity of over 95% and a molar activity of 43-198 GBq/µmol. The preliminary biodistribution study showed the brain uptake in the shaken group was much higher than the control group on day 5 (1.17 %ID/g vs 0.65 %ID/g). The uptake in the brain of the shaken group remained high until day 8 (1.09 %ID/g vs 0.46 %ID/g). On days 11 and 15, the brain uptake of [¹⁸F]GE180 was comparable for both groups. Significant [¹⁸F]GE180 uptake was also observed in heart, lung, kidney, liver, and spleen in both groups. Consistent with the brain uptake pattern, the tracer uptake in these organs was much higher in the shaken group compared to the control group, indicating mild shaking of the rat pups may also cause global peripheral inflammation. Conclusions: The preliminary biodistribution study showed [¹⁸F]GE180 had a much higher uptake in the shaken group of the AHT animal model than the control group early in the study. [¹⁸F]GE180, a TSPO specific radioligand for neuroinflammation and glial cell activation, may be a favorable tracer for noninvasive detection of mild traumatic brain injury in AHT, which still presents a challenge using traditional MRI or CT imaging modality. More studies are ongoing to correlate the biodistribution results to PET imaging and histological analyses.