Development of a gold nanoparticle-functionalized surface plasmon resonance assay for the sensitive detection of monoclonal antibodies and its application in pharmacokinetics

As a prominent human therapeutic, therapeutic monoclonal antibodies (mAbs) have attracted increasing attention in the past decade due to their high targeting specificity, low toxicity, and prolonged efficacy. Systematic pharmacokinetic analysis of mAbs not only largely facilitates the understanding of their biological functions but also promotes the development of therapeutic drug discovery, early clinical trial implementation and therapeutic monitoring. However, the extremely complex nature of biomatrices and the especially low dosages of mAbs make their detection in biomatrices and further pharmacokinetic analysis highly challenging. Therefore, a method capable of reliably, quickly and sensitively quantifying mAbs in biomatrices is urgently needed. Herein, we developed and evaluated an Au NP-functionalized surface plasmon resonance (SPR) assay for C225 (cetuximab) detection and pharmacokinetic analysis in rhesus monkeys. Combining its advantages of label-free pretreatment and amplified signal response, the lower limit of quantitation (LLOQ) of C225 in monkey serum was reduced to 0.0125 μg/mL, and the linear range had an order of magnitude comparable to that of an ELISA-based method. Furthermore, the pharmacokinetics of C225 in rhesus monkeys were studied after intravenous infusions of single doses at 7.5, 24 and 75 mg/kg. The concentration of C225 in monkey serum was detectable after dosing for 720 h. We believe that this new strategy will be applicable as a general protocol for mAb quantification, pharmacokinetic characteristic determination, and toxicokinetic analysis during drug development. SIGNIFICANCE STATEMENT N/A