Comparative Study of a Series of 99mTc(CO)3 Mannosylated Dextran Derivatives for Sentinel Lymph Node Detection

Afroditi Papasavva,Ioanna Roupa,Konstantina Makrypidi,Myrto Ischyropoulou,Christos Kiritsis,Irineos Pilatis,Maria Pelecanou,Minas Papadopoulos,Antonio Shegani,George Loudos,Ioannis Pirmettis

doi:10.3390/molecules26164797

Afroditi Papasavva, Ioanna Roupa + Show 9 more

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https://doi.org/10.3390/molecules26164797

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Abstract

Sentinel lymph node detection (SLND) is rapidly entering common practice in the management of patients with tumors. The introduction of mannose molecules to 99mTc-labeled dextrans, so far, showed that the sentinel node could trap these agents due to their recognition by the mannose receptors of lymph node macrophages. The current study aimed to synthesize, characterize, and biologically evaluate a series of mannosylated dextran derivatives labeled with 99mTc for potential use in SLND. The compounds were designed to have a dextran with a molecular weight of 10–500 kDa as a backbone, S-derivatized cysteines, efficient SNO chelators, and mannose moieties for binding to mannose receptors. They were successfully synthesized, thoroughly characterized using NMR techniques, and labeled with the fac-[99mTc(CO)3]+ synthon. Labeling with high yields and radiochemical purities was achieved with all derivatives. In vivo biodistribution and imaging studies demonstrated high uptake in the first lymph node and low uptakes in the following node and confirmed the ability to visualize the SLN. Among the compounds studied, 99mTc-D75CM demonstrated the most attractive biological features, and in combination with the high radiochemical yield and stability of the compound, its further evaluation as a new radiopharmaceutical for sentinel lymph node detection was justified.

Highlights

Over the last decade, research on developing new radiopharmaceuticals has focused on the selective binding of a radiolabeled biomolecule to a receptor
We present the synthesis and biological evaluation of a series of DCM derivatives employing dextrans of different MW spanning 10–500 kDa in an attempt to develop a 99mTc-DCM product with improved biological characteristics as an sentinel lymph node (SLN) imaging agent
The new dextran derivatives D10CM–D500CM were synthesized and characterized by NMR following the procedures described in detail for DCM20 [23]

Summary

Introduction

Research on developing new radiopharmaceuticals has focused on the selective binding of a radiolabeled biomolecule to a receptor. The biomolecule acts as a vector that transports the radionuclide to the tissue overexpressing the receptor to enable imaging and diagnosis with a SPECT or PET camera or with radiotherapy [1]. The development of diagnostic radiopharmaceuticals for the precise localization of the sentinel lymph node (SLN), the hypothetical first lymph node to receive lymph and metastatic cells from the primary site of the tumor, is actively explored, aiming at identifying affected tissues that require surgical removal. Sentinel lymph node biopsy (SLNB) gradually replaces extensive lymph node removal in patients with cancer, offering more accurate diagnosis and reducing unnecessary lymph node dissection (lymphadenectomy) [3,4,5,6,7]

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