Imaging inflammatory diseases with neutrophil-specific technetium-99m-labeled monoclonal antibody anti-SSEA-1.

ABSTRACT

UNLABELLED Imaging inflammatory diseases with a 99mTc-labeled neutrophil-specific 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)/human PMN) with a high association constant (kd = 10(-11) M). One hundred micrograms of MAb labeled with 10-20 mCi 99mTc either by a direct or DTPA conjugation method were injected intravenously into 12 patients (9 men, 3 women, aged 19-48 yr) with clinical evidence of ongoing inflammatory processes. Vital signs of all patients were recorded before and up to 3 hr following administration of the MAb. HAMA was determined 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 from five patients were analyzed. In nine patients, quantitative organ distribution was determined and radiation dosimetry was calculated. RESULTS: Labeling yields were 94.8% +/- 1.4% and 95.8% +/- 3.5%, respectively. All patients had unequivocally positive images within 3 hr of the MAb injection. Eleven of these were confirmed by other modalities. One patient recovered on antibiotics and was sent home without surgery or other procedures. The lack of radioactivity in the thyroid or gastrointestinal tract indicated that the in vivo stability of the agent was excellent. At 3 hr postinjection, bladder activity in six patients was 1.3% +/- 0.4% of the administered dose. At this time, splenic uptake (7.7% +/- 1.0% ad. dose) and red marrow uptake (14 +/- 1.8%) were lower than those of 111In-WBC. At 49.0% +/- 3.2% administrated dose, liver uptake was at the upper limit with 111In-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 with 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 adverse reaction was detectable in any patient. CONCLUSION: Results are highly encouaging and have prompted us to prepare a kit for instant preparation and to initiate clinical trials.