Size and specificity of radiopharmaceuticals for sentinel lymph node detection.

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 (99m)Tc-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 [(99m)Tc(OH(2))(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.

Parameters optimization defined by statistical analysis for cysteine-dextran radiolabeling with technetium tricarbonyl core.

The objective of this study was the development of a statistical approach for radiolabeling optimization of cysteine-dextran conjugates with Tc-99m tricarbonyl core. This strategy has been applied to the labeling of 2-propylene-S-cysteine-dextran in the attempt to prepare a new class of tracers for sentinel lymph node detection, and can be extended to other radiopharmaceuticals for different targets. The statistical routine was based on three-level factorial design. Best labeling conditions were achieved. The specific activity reached was 5 MBq/µg.

Influence of colloid particle profile on sentinel lymph node uptake.

INTRODUCTION: Particle size of colloids employed for sentinel lymph node (LN) detection is not well studied. This investigation aimed to correlate particle size and distribution of different products with LN uptake. METHODS: All agents (colloidal tin, dextran, phytate and colloidal rhenium sulfide) were labeled with (99m)Tc according to manufacturer's instructions. Sizing of particles was carried out on electron micrographs using Image Tool for Windows (Version 2.0). Biodistribution studies in main excretion organs as well as in popliteal LN were performed in male Wistar rats [30 and 90 min post injection (p.i.)]. The injected dose was 0.1 ml (37 MBq) in the footpad of the left posterior limb. Dynamic images (0-15 min p.i.) as well as static ones (30 and 90 min) were acquired in gamma camera. RESULTS: Popliteal LN was clearly reached by all products. Nevertheless, particle size remarkably influenced node uptake. Colloidal rhenium sulfide, with the smallest diameter (5.1 x 10(-3)+/-3.9 x 10(-3) microm), permitted the best result [2.72+/-0.64 percent injected dose (%ID) at 90 min]. Phytate displayed small particles (<15 microm) with favorable uptake (1.02+/-0.14%ID). Dextran (21.4+/-12.8 microm) and colloidal tin (39.0+/-8.3 microm) were less effective (0.55+/-0.14 and 0.06+/-0.03%ID respectively). Particle distribution also tended to influence results. When asymmetric, it was associated with biphasic uptake which increased over time; conversely, symmetric distribution (colloidal tin) was consistent with a constant pattern. CONCLUSION: The results are suggesting that particle size and symmetry may interfere with LN radiopharmaceutical uptake.