Technetium-99m labelled hydrazinonicotinamido human non-specific polyclonal immunoglobulin G for detection of infectious foci: A comparison with two other technetium-labelled immunoglobulin preparations

Recently a new linker - hydrazinonicotinate (HYNIC) - was introduced for labelling of proteins and peptides with technetium-99m. HYNIC and other linkers have been used for labelling of human non-specific polyclonal immunoglobulin G (hIgG) with Tc-99m for the detection of infections. In this study we compared the tissue distribution of three different Tc-99m-hIgG preparations in groups of five Wistar rats with a focal intramuscular infection with Staphylococcus aureus. We compared Tc-99m-HYNIC-hIgG with Tc-99m-hIgG labelled via the so-called Schwarz method (reduction of disulphide bonds) and with the Tc-99m-labelled commercially available Technescan-HIG. Unlike the HYNIC linker, in the two other labelling methods free sulph-hydryl groups are involved in the binding of Tc-99m. High-performance liquid chromatography analysis of the labelled preparations and of plasma samples revealed aggregate or polymer formation in all three agents; this was least pronounced in the product labelled by means of the Schwarz method. The tested preparations did not show signs of degradation in vitro. The difference in linker chemistry was reflected in the tissue distribution. Thus the biodistribution of Tc-99m-HYNIC-hIgG was significantly different from the distribution of the two other preparations: abscess (1.4%+/-0.2%ID/g), muscle, liver, spleen, plasma, lung, bone marrow, and small intestine concentrations were higher at 24 h p.i.; kidney uptake (1.19%+/-0.08%ID/g) was significantly lower. The abscess-to-plasma and the abscess-to-muscle ratios (0.5 and 11, respectively), however, were in the same range for the three preparations tested. Quantitative analysis of the scintigraphs revealed that the total body clearance of Tc-99m-HYNIC-hIgG was significantly slower than for the other agents. The abscess uptake of Tc-99m-HYNIC-hIgG as a percentage of the remaining body activity was significantly higher. Based on its high abscess uptake, its low uptake in the kidneys and the high percentage of its abscess uptake in relation to the remaining body activity, we conclude that Tc-99m-HYNIC-hIgG seems superior to the two other preparations tested for the detection of infections.