Targeted design of a recombinant tracer for SPECT renal imaging

Area of Science:

• Radiopharmaceutical development
• Molecular imaging
• Renal physiology

Background:

• Robust radiopharmaceuticals require high target uptake and low non-target retention.
• Traditional renal imaging tracers using 99mTc chelation are rapidly excreted, limiting kidney retention time.
• A novel approach is needed for sustained renal tracer presence for effective imaging.

Purpose of the Study:

• To design and evaluate a protein-based radiotracer, PBT-Fc, for targeted kidney imaging.
• To achieve prolonged retention of the tracer within the kidney parenchyma.
• To enhance the detection of kidney pathologies using advanced imaging techniques.

Main Methods:

• Constructed a recombinant fusion protein (PBT-Fc) combining a polybasic PBT segment and an IgG1 Fc segment.
• Labeled the PBT-Fc fusion protein with radionuclide 99mTc.
• Evaluated renal-specificity and imaging performance in rodent models of kidney disease using planar scintigraphy and SPECT.

Main Results:

• [99mTc]-PBT-Fc showed ~95% concentration in the kidney within 10-15 minutes post-injection in mice and rats.
• The tracer exhibited prolonged retention in the kidney for hours with minimal urinary excretion or off-target tissue activity.
• SPECT imaging with [99mTc]-PBT-Fc significantly improved the detection of pathological lesions in various kidney disease models.

Conclusions:

• Exclusive renal retention of [99mTc]-PBT-Fc facilitates static-phase SPECT imaging.
• The tracer achieved submillimeter spatial resolution for kidney alterations in glomerular and tubular disease models.
• This protein-based radiotracer represents a promising tool for advanced renal imaging and diagnostics.