Mapping nephron mass in vivo using positron emission tomography.

Area of Science:

• Biomedical Imaging
• Nephrology
• Radiochemistry

Background:

• Nephron number is critical for kidney health; low nephron endowment or loss increases chronic kidney disease (CKD) susceptibility.
• Current methods for assessing nephron mass are limited, hindering early diagnosis and management of kidney diseases.
• Positron emission tomography (PET) offers high sensitivity for in vivo imaging at low tracer doses, suitable for clinical use.

Purpose of the Study:

• To develop and evaluate a novel PET contrast agent, radiolabeled cationic ferritin (RadioCF), for mapping functioning glomeruli in vivo.
• To assess the ability of RadioCF-PET to distinguish between kidneys with normal and reduced nephron mass.
• To explore the clinical translatability of RadioCF-PET for assessing human kidney nephron mass.

Main Methods:

• Cationic ferritin (CF) was radiolabeled with Cu-64 to create RadioCF.
• RadioCF, radiolabeled noncationic ferritin (RadioNF), and free Cu-64 were injected intravenously into mice.
• PET imaging was performed to assess kidney uptake and specificity of RadioCF in wild-type (WT) and oligosyndactylism (Os^/+) mice, and in a donated human kidney.

Main Results:

• RadioCF specifically bound to kidney glomeruli in mice, unlike RadioNF and free Cu-64.
• RadioCF-PET imaging showed a 21% higher standardized uptake value (SUV) in WT mice compared to Os^/+ mice, reflecting higher glomerular density.
• In a human kidney, RadioCF-PET SUV correlated strongly with glomerular number (R²=0.78) measured by MRI.

Conclusions:

• Radiolabeled cationic ferritin (RadioCF) is a specific and sensitive PET tracer for mapping functioning glomeruli in vivo.
• RadioCF-PET accurately quantifies nephron mass in preclinical models and shows potential for clinical assessment of human kidney health.
• This technology holds promise for early detection and monitoring of kidney diseases linked to nephron number.