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A synthetic macromolecule for sentinel node detection: (99m)Tc-DTPA-mannosyl-dextran
D R Vera1, A M Wallace, C K Hoh
1Departments of Radiology and Surgery and UCSD Cancer Center, University of California, San Diego, La Jolla, California.
Summary
We developed a novel macromolecule, technetium-99m-diethylenetriaminepentaacetic acid (DTPA)-mannosyl-dextran, for improved sentinel lymph node detection. This new radiotracer shows faster clearance from injection sites and better lymph node targeting than current methods.
Area of Science:
- Bioconjugate Chemistry
- Radiopharmaceutical Science
- Nanomedicine
Background:
- Sentinel lymph node (SLN) detection is crucial for cancer staging.
- Current SLN tracers like filtered technetium-99m-sulfur colloid have limitations in clearance and accumulation.
Purpose of the Study:
- To synthesize and evaluate a novel synthetic macromolecule, (99m)Tc-DTPA-mannosyl-dextran, as a receptor-based SLN radiotracer.
- To compare its performance against filtered (99m)Tc-sulfur colloid in preclinical models.
Main Methods:
- A dextran backbone was functionalized with amino groups, DTPA, and mannose.
- The macromolecule was labeled with (99m)Tc and characterized for size, density, and stability.
- Receptor affinity was assessed using Scatchard analysis.
- In vivo studies compared (99m)Tc-DTPA-mannosyl-dextran and filtered (99m)Tc-sulfur colloid for lymph node uptake and injection site clearance in animal models.
Main Results:
- The synthesized (99m)Tc-DTPA-mannosyl-dextran had a molecular weight of 35,800 g/mol and a diameter of 7.1 nm.
- Labeling yields exceeded 98% with high specific activity.
- The tracer demonstrated significantly higher popliteal lymph node extraction (90.1% at 1h) compared to filtered (99m)Tc-sulfur colloid (78.8% at 1h).
- Faster injection site clearance was observed for (99m)Tc-DTPA-mannosyl-dextran.
Conclusions:
- (99m)Tc-DTPA-mannosyl-dextran is a promising receptor-based SLN radiotracer.
- It exhibits favorable properties including rapid injection site clearance and efficient lymph node accumulation.
- This represents a new class of diagnostic agents utilizing a functionalized macromolecular backbone.