Faculty of Physics - University of Bucharest

UNIVERSITY OF BUCHAREST
FACULTY OF PHYSICS

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2024-11-24 10:04

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Conference: Bucharest University Faculty of Physics 2011 Meeting

Section: Biophysics; Medical Physics

Title:

Receptor Targeted Lymphoscintigraphy Using Dextran Macromolecule Derivatives Labelled with 99mTC: in vivo Biological Evaluation

Authors:

Dana Niculae (1), Ioana Patrascu (1), Cosmin Mustaciosu (1), Gabriela Voicu (2)

Affiliation:

Horia Hulubei National Institute for Physics and Nuclear Engineering , Bucharest Magurele, Romania (1)

CI Parhon Institute of Endocrinology, Bucharest, Romania(2)

E-mail

ipatrascu@nipne.ro

Keywords:

radiopharmaceuticals, 99mTC, lymphatic system, sentinel lymph node

Abstract:

Introduction Use of 99mTc in studies for developing cancer specific radiopharmaceuticals offers the possibility of cost effective applications. Numerous radiopharmaceuticals are presently utilized for sentinel node detection: 99mTc-sulfur colloid, filtered 99mTc-sulfur colloid and different microcolloids of 99mTc-labelled albumin but none of these agent have ideal properties regarding the selective accumulation in sentinel node, they are uptaken also of distal lymph node. The lymphoscintigraphy agent requires a high density of receptor substrate sites to achieve a receptor affinity required for proper sentinel node detection. The solution is given by receptor-binding radiopharmaceuticals which can be synthesized with high specific activities, compatible with typical target tissue receptor densities. Aim The radiolabelling of the mannosyl-cysteine-dextran macromolecules with 99mTc (Dextran-propyl-S-Cysteine, Dextran-S-Cysteine-Mannose, Dextran-S-Cysteamine-Mannose, Dextran-amine-Pyrazole-Mannose, Dextran-Cysteine-Cysteine-Mannose) resulting in a high purity and stability radiolabelled conjugate, suitable for sentinel node detection with low distal lymph accumulation, as well as their in vivo biological evaluation are the proposed aims of this study. Results Different radiolabelling strategies, including novel 99mTc cores, were evaluated in order to select and optimize the most efficient and specific one. The quality control of radiolabeled conjugates using TLC and HPLC was performed; the RCPs of the probes were ranged in the interval 93-99%. The biological evaluation (ex-vivo biodistribution and specific uptake) was performed in Wistar rats at 15, 30 and 60 min post injection. The biological data shows a rapid and highly specific sentinel node accumulation, up to 11% ID, and a very good sentinel node extraction with respect to the second node in the chain up to 94% at 1h post injection.