Size and specificity of radiopharmaceuticals for sentinel lymph node detection

Abstract

Background Biological performance of radiotracers for sentinel node detection analyzed in the light of molecular design and dimension is not widely available. Purpose To evaluate the effect of dextran molecular size and the presence of tissue-binding units (mannose) within the model of 99mTc-carbonyl conjugate for sentinel lymph node detection. Material and Methods Four dextran conjugates with and without mannose in the chemical backbone were included. All polymers were radiolabeled using the precursor [99mTc(OH2)3(CO)3]+. Radiolabeling conditions targeted the best radiochemical purity and specific activity for each radiopharmaceutical, and partition coefficients were also defined. Lymphoscintigraphy and ex-vivo biodistribution in popliteal lymph node, liver and kidneys were performed in Wistar rats. The effects of molecular weight and mannose presence were assessed by a two-level factorial design. Results Radiochemical purity was indirectly related to molecular weight and presence of mannose in the polymer structure. All products were able to detect popliteal lymph node, however, uptake was strongly influenced by use of mannose (4-fold higher). Excretion was similarly modulated by differences in molecular weight. Mannose-enhanced lymph node uptake and higher molecule size in the range under study benefitted lymphoscintigraphic performance. Conclusion Screening of radiopharmaceuticals for lymphoscintigraphy might improve with attention to the mentioned physico-chemical features of the molecule.