IMAGING INFLAMMATORY DISEASES WITH NEUTROPHIL-SPECIFIC TC-99M-LABELEDMONOCLONAL-ANTIBODY ANTI-SSEA-1

Imaging inflammatory diseases with a Tc-99m-labeled neutrophil-specifi c agent that can be injected directly intravenously continues to be a challenge. Methods: The antibody, anti-SSEA-1, chosen from studies of 10 neutrophil-specific MAbs, recognizes CD-15 antigens (5.1 x 10(5)/hu man PMN) with a high association constant (kd = 10(-11) M). One hundre d micrograms of MAb, labeled with 10-20 mCi Tc-99m, either by a direct or DTPA conjugation method were injected intravenously into 12 patien ts (9 men, 3 women, aged 19-48 yr) with clinical evidence of ongoing i nflammatory processes. Vital signs of all patients were recorded befor e and up to 3 hr following administration of the MAb. HAMA was determi ned in two patients. Anterior and posterior spot views and whole-body images were obtained. All patients except one underwent biopsy, US or CT examinations and/or surgical procedures. Blood samples collected fr om five patients were analyzed. In nine patients, quantitative organ d istribution was determined and radiation dosimetry was calculated. Res ults: Labeling yields were 94.8% +/- 1.4% and 95.8% +/- 3.5%, respecti vely. All patients had unequivocally positive images within 3 hr of th e MAb injection. Eleven of these were confirmed by other modalities. O ne patient recovered on antibiotics and was sent home without surgery or other procedures. The lack of radioactivity in the thyroid or gastr ointestinal tract indicated that the in vivo stability of the agent wa s excellent. At 3 hr postinjection, bladder activity in six patients w as 1.3% +/- 0.4% of the administered dose. At this time, splenic uptak e (7.7% +/- 1.0% ad. dose) and red marrow uptake (14 +/- 1.8%) were lo wer than those of In-111-WBC. At 49.0% +/- 3.2% administered dose, liv er uptake was at the upper limit with In-111-WBC uptake. Renal uptake was only 2.4% +/- 0.03% administered dose. At 2 hr postinjection, 14% to 51% of the radioactivity was associated with PMN. Radioactivity wit h lymphocytes was 0.7% to 10.9%, 1.2% to 4.3% with platelets and 1.1% to 2.4% with RBC. No HAMA were detectable in either patient, and no ad verse reaction was detectable in any patient. Conclusion: Results are highly encouaging and have prompted us to prepare a kit for instant pr eparation and to initiate clinical trials.