99mTc-Fanolesomab: affinity, pharmacokinetics and preliminary evaluation

Localization of infection is critical for both diagnosis and treatment. Several radioactive compounds such as (67)Gallium citrate, (111I)ndium and (99m)Technetium-labeled leukocytes, peptides and antibodies have been used to localize sites of bacterial infection and phlegmons when anatomical imaging techniques failed. With labeled leukocytes the major concern besides the cost, was the in vitro procedure requiring more than 2 h and trained personnel to handle blood samples. Such limitations paved the way for the emergence of new agents like human immunoglobulin, interleukin-1, peptides and monoclonal antibodies. Following the intensive study of 10 monoclonal antibodies the anti SSEA-1 antibody specific for CD15 antigen was found to have a high Kd value of 1.6x10(-11) M for human neutrophils. Labeling of anti CD15 antibody (NeutroSpec) with (99m)Tc and its FDA approval was a boon to diagnostic imaging as it promised to eliminate many of the well known drawbacks of the in vitro WBC labeling. This antibody has a large number of antigenic binding sites: 5.1x10(5) per circulating human neutrophil. It has been established that very little CD15 antigen is expressed on the other blood cell lines. Upon intravenous administration to patients there was no adverse reaction except in those with underlying cardiovascular compromise or chronic pulmonary obstructive disease. Another advantage is that, this particular monoclonal antibody has not produced significant human antimouse antibody in research volunteers and patients. Twenty-four hour imaging, SPECT or planar was not required. The following pages describe the various stages of the research activity carried out towards NeutroSpec.