TC-99M LABELED HYDRAZINONICOTINAMIDO HUMAN NONSPECIFIC POLYCLONAL IMMUNOGLOBULIN-G FOR DETECTION OF INFECTIOUS FOCI - A COMPARISON WITH 2 OTHER TECHNETIUM-LABELED IMMUNOGLOBULIN PREPARATIONS

Recently a new linker - hydrazinonicotinate (HYNIC) - was introduced f or labelling of proteins and peptides with technetium-99m. HYNIC and o ther linkers have been used for labelling of human non-specific polycl onal immunoglobulin G (hIgG) with Tc-99m for the detection of infectio ns. In this study we compared the tissue distribution of three differe nt Tc-99m-hIgG preparations in groups of five Wistar rats with a focal intramuscular infection with Staphylococcus aureus. We compared Tc-99 m-HYNIC-hIgG with Tc-99m-hIgG labelled via the so-called Schwarz metho d (reduction of disulphide bonds) and with the Tc-99m-labelled commerc ially available Technescan-HIG. Unlike the HYNIC linker, in the two ot her labelling methods free sulph-hydryl groups are involved in the bin ding of Tc-99m. High-performance liquid chromatography analysis of the labelled preparations and of plasma samples revealed aggregate or pol ymer formation in all three agents; this was least pronounced in the p roduct labelled by means of the Schwarz method. The tested preparation s did not show signs of degradation in vitro. The difference in linker chemistry was reflected in the tissue distribution. Thus the biodistr ibution of Tc-99m-HYNIC-hIgG was significantly different from the dist ribution of the two other preparations: abscess (1.4%+/-0.2%ID/g), mus cle, liver, spleen, plasma, lung, bone marrow, and small intestine con centrations 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-mu scle ratios (0.5 and 11, respectively), however, were in the same rang e for the three preparations tested. Quantitative analysis of the scin tigraphs revealed that the total body clearance of Tc-99m-HYNIC-hIgG w as significantly slower than for the other agents. The abscess uptake of Tc-99m-HYNIC-hIgG as a percentage of the remaining body activity wa s significantly higher. Based on its high abscess uptake, its low upta ke in the kidneys and the high percentage of its abscess uptake in rel ation to the remaining body activity, we conclude that Tc-99m-HYNIC-hI gG seems superior to the two other preparations tested for the detecti on of infections.