RESUMO
Positron emission tomography (PET) targeting translocator protein 18 kDa (TSPO) can be used for the noninvasive detection of neuroinflammation. Improved in vivo stability of a TSPO tracer is beneficial for minimizing the potential confounding effects of radiometabolites. Deuteration represents an important strategy for improving the pharmacokinetics and stability of existing drug molecules in the plasma. This study developed a novel tracer via the deuteration of [18F]LW223 and evaluated its in vivo stability and specific binding in neuroinflammatory rodent models and nonhuman primate (NHP) brains. Compared with LW223, D2-LW223 exhibited improved binding affinity to TSPO. Compared with [18F]LW223, [18F]D2-LW223 has superior physicochemical properties and favorable brain kinetics, with enhanced metabolic stability and reduced defluorination. Preclinical investigations in rodent models of LPS-induced neuroinflammation and cerebral ischemia revealed specific [18F]D2-LW223 binding to TSPO in regions affected by neuroinflammation. Two-tissue compartment model analyses provided excellent model fits and allowed the quantitative mapping of TSPO across the NHP brain. These results indicate that [18F]D2-LW223 holds significant promise for the precise quantification of TSPO expression in neuroinflammatory pathologies of the brain.
RESUMO
BACKGROUND: Cladosporium and Corynespora cassiicola (C. cassiicola) infections rarely occur in humans. Mutations in human caspase recruitment domain protein 9 (CARD9) are reported to be associated with fungal diseases. Pulmonary Cladosporium infection coexisting with subcutaneous C. cassiicola infection in a patient with a CARD9 mutation has not been reported in the literature. CASE SUMMARY: A 68-year-old male patient was hospitalized for hypertrophic erythema and deep ulcers on the left upper extremity. He was diagnosed with pneumonia caused by Cladosporium, as identified through bronchoalveolar lavage fluid analysis, and deep dermatophytosis caused by C. cassiicola, as identified through morphological characteristics of the wound secretion culture. He underwent antifungal therapy (voriconazole) and recovered successfully. He carried two mutations in CARD9 (chr9:139266425 and chr9:139262240) and was therefore susceptible to fungal infections. CONCLUSION: This case study is the first to report the coexistence of pulmonary Cladosporium infection and subcutaneous C. cassiicola infection in a patient with CARD9 mutation. Our findings will be helpful in enriching the phenotypic spectrum of fungal infections underlying CARD9 deficiency.