99m Tc anti-CD 15 monoclonal antibody (LeuTech) imaging improves diagnostic accuracy and clinical management in patients with equivocal presentation of appendicitis

Approximately 250,000 cases of acute appendicitis are diagnosed each year in the United States and many more patients with abdominal pain masquerading as appendicitis are evaluated in emergency departments and doctors offices. Appendicitis is the most common cause of acute abdominal pain requiring surgical intervention, and carries an associated mortality of 0.8% to 8%. 1-5 The incidence is highest in the second and third decades of life, but appendicitis may occur at any age. 4 In the presence of classic signs and symptoms of acute appendicitis, a quick and accurate diagnosis can be made based on history and physical examination alone. 5-7 However, as many as 50% of patients do not exhibit characteristic signs and symptoms. 4,6 In these equivocal patients, the diagnosis of appendicitis is difficult, delayed, and frequently inaccurate. 4 Complications including perforation, peritonitis, and death may occur with delayed diagnosis, particularly in the very young and in the elderly. 6 As many as 45% of cases are misdiagnosed, resulting in unnecessary hospitalizations and sometimes unnecessary surgery. 6 Surgical exploration has been reported to be negative in 10% to 30% of patients with a preoperative diagnosis of appendicitis. 8,9 More accurate diagnosis and reduction in unnecessary hospitalization or surgery in patients with an equivocal presentation would result in improved clinical outcomes and conservation of hospital resources. The currently available radioisotope infection imaging technique using 99mTc-HMPAO labeled white blood cells (WBC) is very sensitive for detecting appendicitis. 10-13 The primary disadvantages of radiolabeled WBC imaging include a lengthy preparation time of 2 hours and sometimes longer if an off site radiopharmacy is used, the requirement of ex vivo white blood cell radiolabeling, the potential for external blood contamination and misadministration, personnel exposure to blood borne infection such as hepatitis and HIV, and the relatively high cost and technical demand of the procedure. Because of these disadvantages, very few medical centers are capable of using radiolabeled WBC imaging for the diagnosis of appendicitis. Monoclonal antibodies specific for surface antigens on neutrophils address many of these disadvantages and may be useful infection imaging agents when labeled with a radionuclide. 14 99mTc-labeled anti-CD 15 monoclonal antibody (LeuTech; Palatin Technologies, Inc., Princeton, NJ); also known as 99mTc-anti-stage-specific embryonic antigen [SSEA]-1 monoclonal antibody) binds avidly to surface CD 15 antigens that are expressed on human neutrophils in large numbers. 15-17 As a result of the in vivo systemic administration of radiolabeled LeuTech, radioactivity becomes concentrated in areas of infection or inflammation; thus, the need to withdraw blood from a patient to label WBC’s ex vivo is eliminated and the time required to perform the test is reduced significantly. In a prospective pilot study, we performed LeuTech scans on 49 patients with equivocal presentation of appendicitis. 18 The results were encouraging with sensitivity and negative predictive values of 100%. A multicenter clinical trial was undertaken to confirm these preliminary results. This paper reports the results from this prospective, multicenter trial. The aim of this study was to further evaluate and confirm the efficacy and safety of LeuTech scintigraphy for diagnosis of acute appendicitis in patients presenting with equivocal signs and symptoms at multiple centers and in a larger population. In addition, the potential impact of LeuTech imaging on intended patient management was assessed.