A synthetic macromolecule for sentinel node detection: 99mTc-DTPA-mannosyl-dextran

D. R. Vera, A. M. Wallace, C. K. Hoh, R. F. Mattrey

Research output: Contribution to journalArticlepeer-review

156 Scopus citations


We report the synthesis and preliminary biologic testing of a synthetic macromolecule, 99mTc-diethylenetriaminepentaacetic acid (DTPA)-mannosyl-dextran, for sentinel node detection. Methods: Synthesis started with a 2-step process that attaches a high density of amino-terminated leashes to a dextran backbone. Allyl-bromide was reacted with pharmaceutical-grade dextran to yield allyl-dextran. After diafiltration with water, filtration, and lyophilization, the product was reacted with aminoethanethiol and ammonium persulfate. The resulting amino-conjugated dextran was dialyzed, filtered, and lyophilized. The mixed anhydride method was used to attach DTPA; after dialysis, filtration, and lyophilization, 2-imino-2-methoxyethyl-1-D-mannose was used to attach the receptor substrate. The molecular diameter was measured by dynamic light scattering. Amino, mannose, and DTPA densities were measured by trinitrobenzene sulfonate assay, sulfuric acid/phenol assay, and inductively coupled plasma spectroscopy of gadolinium-DTPA-mannosyl-dextran, respectively. Receptor affinity was measured by Scatchard assay of rabbit liver. Axillary, popliteal, and iliac lymph nodes and each injection site were assayed for radioactivity at 1 and 3 h after injection of approximately 3.7 MBq (0.050 mL) 99mTc-DTPA-mannosyl-dextran (0.22 nmol) or filtered 99mTc-sulfur colloid into the foot pads. Four animals were studied at each time point. Results: DTPA-mannosyl-dextran had a molecular weight of 35,800 g/mol and a molecular diameter of 7.1 nm. The final amine, mannose, and DTPA densities were 23, 55, and 8 mol per dextran. Labeling yields were in excess of 98% and stable for 6 h. Specific activities of 74 × 106 GBq/mol were achieved. The equilibrium dissociation constant for binding to the mannose-terminated glycoprotein receptor was 0.12 ± 0.07 nmol/L. The popliteal extraction at both 1 h and 3 h was significantly (P < 0.05) higher for 99mTc-DTPA-mannosyl-dextran (90.1% ± 10.7% and 97.7% ± 2.0%, respectively) than for filtered 99mTc-sulfur colloid (78.8 ± 6.5 and 67.4% ± 26.8%, respectively). 99mTc-DTPA-mannosyl-dextran exhibited significantly faster injection site clearance than did filtered 99mTc-sulfur colloid. The 99mTc-DTPA-mannosyl-dextran percentage injected dose (%ID) for the front and rear paws was 52.6 ± 10.5 and 52.3 ± 8.0 at 1 h and 45.7 ± 8.5 and 43.6 ± 8.2 at 3 h after administration. The filtered 99mTc-sulfur colloid %ID for the front and rear paws was 70.4 ± 11.0 and 66.3 ± 15.1 at 1 h and 55.5 ± 7.8 and 66.9 ± 8.5 at 3 h. Lymph node accumulation of each agent at either 1 or 3 h was not significantly different. Conclusion: 99mTc-DTPA-mannosyl-dextran is a receptor-based sentinel node radiotracer that exhibits the desired properties of rapid injection site clearance and low distal node accumulation. This molecule is the first member of a new class of diagnostic agents based on a macromolecular backbone with a high density of sites for the attachment of substrates and imaging reporters.

Original languageEnglish (US)
Pages (from-to)951-959
Number of pages9
JournalJournal of Nuclear Medicine
Issue number6
StatePublished - 2001


  • DTPA-mannosyl-dextran
  • Receptor-binding radiopharmaceutical
  • Sentinel node
  • Tc

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging


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