Tc-Labeled mannosylated dextran DCM20

Tc-Labeled mannosylated dextran DCM20, abbreviated as Tc(CO)-DCM20, is a dextran derivative bearing -derivatized cysteine chelator and mannose moieties. Tc(CO)-DCM20 was synthesized by Pirmettis et al. for sentinel lymph node (SLN) detection (1). SLN is defined as the first node in the lymphatic basin that receives the primary lymphatic flow. The concept of SLN is embedded with the notion that the metastatic spread of solid tumors through lymphatic vessels follows a predictable pattern, i.e., tumor cells metastasize to the first lymph node encountered by lymphatic draining from the primary tumor (the SLN), followed by the second- and third-tier lymph nodes; being able to determine the status of the SLN with or without metastatic involvement would allow accurate prediction of the status of the entire regional lymphatic basin draining the tumor (2). Based on this concept, a SLN free from tumor metastasis would exclude tumor spread to the at-risk regional lymphatic basin, rendering nodal basin dissection unnecessary and avoiding the immediate and late complications caused by nodal dissection (3). The concept of SLN has now been widely accepted in clinical practice, and the technology for guided SLN biopsy has been evolving rapidly. Compared with other methods, γ-probe–guided SLN biopsy appears to be more cost-effective, and substantial work has been done in developing optimal imaging techniques and radiotracers to visualize the lymphatic channels leading from the site of tracer administration to the corresponding lymph nodes and to identify the SLN encountered along the lymphatic pathway (2, 3). Currently, three types of radiocolloid preparations are commonly used for lymphoscintigraphy combined with intraoperative γ-probe SLN identification. The Tc-sulfur colloid is the most commonly used probe in the United States (2). The probes are given through peritumoral, periareolar, or dermal injection; from the injection site, the probe particles migrate into the lymphatic vessels by passive diffusion. For most probes, intranodal retention is a process of active, saturable phagocytosis of the macrophages lining the sinusoid spaces of lymph nodes (4, 5). The particle size and surface characteristics of probes influence not only the rate of colloid drainage from the injection site to the lymphatic capillaries but also the phagocytosis by lymph node macrophages. Particles <5 nm easily leak into the bloodstream, whereas particles >100 nm are often trapped in the interstitial space, resulting in masking of the SLN (1, 2, 6). Studies have shown that introduction of mannose molecules to Tc-labeled macromolecules like albumin, polylysine, and dextrans enhances the retention of these probes in the SLN in a saturable mode because of the recognition by the mannose receptors of lymph node macrophages, even though the particles are only a few nanometers in size (7, 8). Pirmettis et al. synthesized a mannosylated nanocompound DCM20, which has a dextran backbone, -derivatized cysteines as a chelator for labeling with the [Tc(CO)] core, and mannose moieties for binding with mannose receptors (1). The radiolabeled DCM20 (Tc(CO)-DCM20) exhibited fast injection site clearance and high uptake and retention in the SLN. This chapter summarizes the data obtained with Tc(CO)-DCM20.