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A Synthetic Macromolecule for Sentinel Node Detection: ^99mTc-DTPA-Mannosyl-Dextran

Departments of Radiology and Surgery and UCSD Cancer Center, University of California, San Diego, La Jolla, California

View larger version (15K): [in a new window]   FIGURE 1. Covalent attachment of amino-terminated leashes to dextran hydroxyl groups is 2-step process, which prevents dextran cross-linking. DMSO = dimethyl sulfoxide.

View larger version (19K): [in a new window]   FIGURE 2. Attachment to amino-terminated leashes of chelator, DTPA (A), and receptor substrate, mannose (B).

View larger version (15K): [in a new window]   FIGURE 3. DTPA-mannosyl-dextran amine (NN), mannose (NM), and DTPA (ND) densities were 23, 55, and 8 mol per dextran. Average molecular weight was 35,800 g/mol, and mean molecular diameter was 7.1 nm.

View larger version (15K): [in a new window]   FIGURE 4. Standing gel chromatography of 99mTc-DTPA-mannosyl-dextran showed absence of reduced unbound 99mTc.

View larger version (16K): [in a new window]   FIGURE 5. Fast protein liquid chromatography 6 h after labeling showed absence of polymeric dextran and unbound 99mTc (absorbance, black line; activity, gray line). Vo = void volume.

View larger version (21K): [in a new window]   FIGURE 6. Percentage bound measurements through ITLC showed high 99mTc-DTPA-mannosyl-dextran labeling stability for at least 6 h (A) and approximately 10% loss in percentage bound after 99mTc-sulfur colloid filtration (B). B contains results of 3 labeling experiments. = ITLC results from 4 labeling experiments without purification; = ITLC results from G-25SF–purified 99mTc-DTPA-mannosyl-dextran.

View larger version (13K): [in a new window]   FIGURE 7. In vitro assay of 99mTc-DTPA-mannosyl-dextran binding to liver measured equilibrium dissociation constant, KD, of 0.12 ± 0.07 nmol/L. [B] = bound concentration; B/F = bound-to-free ratio.