In this presentation we focus on understanding structure-activity relationships governing renal of biologics. We highlight the use of imaging as a valuable method/tool to preclinically assess molecular clearance properties. In addition to monitoring systemic exposure, we assessed molecular shape by electron microscopy (EM) and kidney uptake by single photon emission computed tomography (SPECT) on a small library of antibody formats with varied shapes and hinge flexibilities. Our findings demonstrate that molecular shape and hinge flexibility are major drivers in the renal clearance of biologics. Understanding how renal filtration affects pharmacokinetics and distribution of biologics is critical, especially in patients with impaired renal function.
Recognize that renal filtration of biologics can affect systemic exposure, and thereby pharmacodynamic response.
Understand how shape and flexibility of the antibody may affect its renal filtration.
Appreciate the practicality of using pre-clinical SPECT imaging as a tool to assess kidney clearance of biologics.
Recognize the limitations of an arbitrary molecular weight-based cutoff for renal filtration.