Pre-clinical Imaging of Invasive Candidiasis Using ImmunoPET/MR.

摘要: The human commensal yeast Candida is the fourth most common cause of hospital-acquired bloodstream infections, with albicans accounting for majority >400,000 life-threatening infections annually. Diagnosis invasive candidiasis (IC), a disease encompassing candidemia (blood-borne infection) and deep-seated organ major challenge since clinical manifestations are indistinguishable from viral, bacterial other fungal diseases, diagnostic tests biomarkers in such as PCR, ELISA, pan-fungal β-D-glucan lack either standardization, sensitivity, or specificity. Blood culture remains gold standard diagnosis, but test sensitivity poor turn-around time slow. Furthermore, cultures can only be obtained when resides bloodstream, samples recovered hematogenous often yielding negative results. Consequently, there pressing need that allows identification metastatic foci without biopsy. Here, we report development highly specific mouse IgG3 monoclonal antibody (MC3) binds to putative β-1,2-mannan epitope present high molecular weight mannoproteins phospholipomannans on surface hyphal morphotypes C. albicans, its use [64Cu]NODAGA-labeled tracer whole-body pre-clinical imaging using antibody-guided positron emission tomography magnetic resonance (immunoPET/MRI). When used intravenous (i.v.) model faithfully mimics disseminated humans, [64Cu]NODAGA-MC3 accurately detects kidney, principal site blood-borne this model. Using strain emerging pathogen auris reacts MC3 vitro, which non-infective i.v. challenged mice, demonstrate accuracy diagnosing vivo. This study demonstrates principle detection deep IC, tissue