ABSTRACT
In this work, we develop recombinant human cationic ferritin (rHCF) as a contrast agent to detect glomeruli in the kidney using positron emission tomography (PET). We first expressed recombinant human ferritin (rHF) in E. coli and then functionalized and radiolabeled it with Copper-64 (64Cu) to form 64Cu-rHCF. Intravenously injected 64Cu-rHCF bound to kidney glomeruli and was detected by PET. A subchronic toxicity study after an intravenous injection of rHCF revealed no significant toxicity. The development of rHCF is an important step toward the potential clinical translation of CF to detect the nephron number in humans.
ABSTRACT
Cationic ferritin (CF) has been developed as a multimodal, targeted imaging tracer to directly detect and map nephrons in the kidney in vivo. Direct detection of functional nephrons provides a unique, sensitive biomarker to predict or monitor kidney disease progression. CF has been developed to map functional nephron number from magnetic resonance imaging (MRI) or positron emission tomography (PET). Previous preclinical imaging studies have used non-human-derived ferritin and commercial formulations that must still be developed for translation to clinical use. Here we describe the reproducible formulation of CF (either derived from horse or from human recombinant ferritin) optimized for intravenous injection and radiolabeling by PET. The human recombinant heteropolymer ferritin is spontaneously assembled in liquid culture (Escherichia coli, E. coli) and modified to form human recombinant cationic ferritin (HrCF) to mitigate potential immunologic reactions for use in humans.