Design and Synthesis of 99mTcN-Labeled Dextran-Mannose Derivatives for Sentinel Lymph Node Detection

Abstract

Background: New approaches based on the receptor-targeted molecular interaction have been recently developed with the aim to investigate specific probes for sentinel lymph nodes. In particular, the mannose receptors expressed by lymph node macrophages became an attractive target and different multifunctional mannose derivate ligands for the labeling with 99mTc have been developed. In this study, we report the synthesis of a specific class of dextran-based, macromolecular, multifunctional ligands specially designed for labeling with the highly stable [99mTc≡N]2+ core. Methods: The ligands have been obtained by appending to a macromolecular dextran scaffold pendant arms bearing a chelating moiety for the metallic group and a mannosyl residue for allowing the interaction of the resulting macromolecular 99mTc conjugate with specific receptors on the external membrane of macrophages. Two different chelating systems have been selected, S-methyl dithiocarbazate [H2N‒NH‒C(=S)SCH3=HDTCZ] and a sequence of two cysteine residues, that in combination with a monophosphine coligand, are able to bind the [99mTc≡N]2+ core. Conclusions: High-specific-activity labeling has been obtained by simple mixing and heating of the [99mTc≡N]2+ group with the new mannose-dextran derivatives.

Metal-Polymer Complexes of Gallium/Gallium-68 with Copolymers of N-Vinylpyrrolidonewith N-Vinylformamideand N-Vinyliminodiacetic Acid: A Hint for Radiolabeling of Water-Soluble Synthetic Flexible Chain Macromolecules

“…In order to achieve the maximal accumulation at tumor sites, these macromolecules should demonstrate prolonged circulation time in blood, and should not be accumulated in non-target organs in noticeable amounts; they should have controlled dimensions (for effective localization in cells), and be easily cleared from the organism. Нerewith, flexible chain synthetic water-soluble polymers can be considered as promising objects for targeted radionuclide transport [15,16]. For example, mannosylateddextrans decorated with diethylenetriaminepentaacetic acid (DTPA) chelation units and labeled with 99m Tc are adopted in clinical practice for visualization of defeated lymph nodes under the trade name "Lymphoseek" TM [17].…”

The Pharmaceutical Technology Approach on Imaging Innovations from Italian Research

“…In the context of polysaccharide-based imaging agents, Boschi et al [ 27 ] developed an interesting class of dextran-mannose multifunctional ligands, which were conceived for binding to the [ 99m TcN] 2+ group [ 108 ], being the Tc(V) nitrido complexes widely investigated in the search of new 99m Tc-radiopharmaceuticals [ 109 ]. These multifunctional ligands were conceived for sentinel lymph node detection: actually, sentinel lymph nodes are the first to receive lymphatic drainage and metastatic cells from primary tumors; therefore, their accurate identification might be crucial for establishing the tumor staging and the extension of surgical intervention.…”

Nitrido Technetium-99 m Core in Radiopharmaceutical Applications: Four Decades of Research

“…A very convenient tridentate [SˆNˆS] 2− chelating system is provided by the combination of two terminal cysteine aminoacids (Cys-Cys). The bioactive molecule can be conjugated to the backbone of one Cys group [142,143]. Another chelating agent used for obtaining a "3 + 1" system is the HDTCZ.…”