Project Title: Rationally Designed, Target-specific Imaging Probes for Nephro-urology Diagnoses
Project Summary
The project focuses on novel design and testing of kidney-specific probes for radionuclide renal
imaging. Unlike existing standard-of-care tracers used in the clinic that rely on passive uptake and
clearance mechanisms, our recombinant probes are based on targeted design for mapping kidney
functions, including filtration at the glomerulus and protein sorting at the proximal tubule. This approach
enables functional renal imaging with molecular specificity. We adapted a fusion strategy in designing the
probes, in which we joined modular segments of selected plasma proteins to form new hybrid probes.
These modular segments are the functional units that can individually interact with their cognate renal
receptors. Accordingly, it is anticipated that each probe will follow a guided intrarenal passage and
sequentially interactions with intended receptors. This novel approach holds promise, as demonstrated in
proof-of-concept studies and will continue to be pursued, for measuring distinct functions of the kidney. We
will accomplish our research goal via three interconnected and synergistic Specific Aims, which are
designed for measuring critical aspects of the renal function and pathophysiology, including glomerular
filtration and tubular reuptake (Aim 1), glomerular density (Aim 2), and the early pathological changes in
the filtration barrier (Aim 3). The studies will be conducted in acute and chronic settings as appropriate
using relevant kidney disease models such as ischemic/reperfusion injury, nephrotoxicity, hypertension
and autoimmunity, which are representative of common renal diseases in humans. Overall, our new probes
are intended for directly addressing the needs for early and specific markers of renal diseases. The imaging
data from these probes will provide important mechanistic insights for advancing the technologies toward
their ultimate translation to patient care.