Imaging of fungal infections

摘要： 我们一直在寻求三种主要方法来开发用于活体诊断的放射性标记真菌特异性配体： 1.现有配体的评价：我们已经测试了18F-脱氧山梨醇，它被描述为革兰氏阴性菌的合适配体。我们发现曲霉菌有轻微的摄取，但这还不够高，不足以准确诊断。我们在2022年的《真菌杂志》上发表了我们的研究结果。 2.放射性标记糖的评价：我们目前正在评价两种潜在的配体：18F-纤维二糖和海藻糖。结果待定。 3.使用针对甲壳素和层粘连蛋白的放射性标记抗体和纳米抗体：我们目前正在评估针对真菌细胞成分层粘连蛋白和Fab片段的全抗体。虽然我们在真菌感染中发现了标记抗体的摄取，但我们也看到了相同程度的同型抗体摄取，这表明抗体太大，最终由于内皮通透性增加而在炎症区域积聚。当我们使用Fab抗体片段时，我们发现感染的动物摄取了Fab，而未感染的动物没有摄取。同型Fab在感染和未感染的动物中均不积聚。我们还在评估单链抗体(纳米抗体)，以提高针对真菌感染的特异性。结果待定。

Summary: We have been pursuing three main approaches to developing radiolabeled fungal specific ligands for in vivo diagnosis: 1. Evaluation of existing ligands: we have tested 18F-fluorodeoxysorbitol which has been described as an appropriate ligand for gram negative bacteria. We found that there was mild uptake by aspergillus species however this was not high enough for accurate diagnosis. We published our results in J Fungi in 2022. 2. Evaluation of radiolabeled sugars: we are currently evaluating two potential ligands: 18F-Cellobiose and Trehalose. Results pending. 3. Using radiolabeled antibodies and nanobodies specific for chitin and laminarin: we are currently evaluating a full antibody against fungal cell component laminarin as well as Fab Fragment. Although we found uptake of labeled antibody in fungal infection, we also saw uptake of an isotype antibody to the same extent suggesting antibodies are too large and end up accumulating nonspecifically in areas of inflammation due to increased endothelial permeability. When we used Fab antibody fragments, we found uptake of the Fab in the infected animals but no uptake in uninfected animals. Isotype Fab did not accumulate neither in infected nor in uninfected animals. We are also evaluating single chain antibodies (nanobodies) to improve the specificity of targeting fungal infections. Results pending.