Article 1

Clinical Utility of External Immunoscintigraphy With the IMMU-4 Technetium-99m Fab' Antibody Fragment in Patients Undergoing Surgery for Carcinoma of the Colon and Rectum: Results of a Pivotal, Phase III Trial

Frederick L. Moffat, Jr., MD, Carl M. Pinsky, MD, Luz Hammershaimb, MD, Nicholas J. Petrelli, MD, Yehuda Z. Patt, MD, Frederick S. Whaley, MD and David M. Goldenberg, ScD, MD, for the Immunomedics Study Group

Purpose: To assess the performance and the potential clinical impact of a new antibody imaging agent, CEA-Scan (Immunomedics Inc, Morris Plains, NJ), in 210 presurgical patients with advanced recurrent or metastatic colorectal carcinomas.

Methods: CEA-Scan, an anti-carcinoembryonic antigen (CEA) Fab' antibody fragment labeled with technetium-99m-pertechnetate (^99mTc), was injected intravenously (IV). and external scintigraphy was performed 2 to 5 and 18 to 24 hours later. Imaging with conventional diagnostic modalities (CDM) was also performed, and findings were confirmed by surgery and histology.

Results: The sensitivity of CEA-Scan was superior to that of CDM in the extrahepatic abdomen (55% v 32%; P= .007) and pelvis (69% v 48%; P= .005), and CEA-Scan findings complemented those of CDM in the liver. Among 122 patients with known disease, the positive predictive value was significantly higher when both modalities were positive (98%) compared with each alone (68% to 70%), potentially obviating the need for histologic confirmation when both tests are positive. Imaging accuracy also was significantly improved by adding CEA-Scan to CDM. In 88 patients with occult cancer, imaging accuracy was enhanced significantly by CEA-Scan combined with CDM (61% v 33%). Potential clinical benefit from CEA-Scan was demonstrated in 89 of 210 patients. Only two patients developed human antimouse antibodies (HAMA) to CEA-Scan after a single injection, and none of the 199 assessable patients after two injections.

Conclusion: CEA-Scan affords high-quality, same-day imaging, uses an inexpensive and readily available radionuclide, adds clinically significant information in assessing extent and location of disease in colorectal cancer patients, and only rarely induces a HAMA response.