Imaging with indium111-labeled anticarcinoembryonic antigen monoclonal antibody ZCE-025 of recurrent colorectal or carcinoembryonic antigen-producing cancer in patients with rising serum carcinoembryonic antigen levels and occult metastases.

Abstract

We tested whether nuclear imaging with indium111 (111In)-labeled murine monoclonal (MoAb) anticarcinoembryonic antigen (anti-CEA) ZCE-025 antibody could detect recurrent disease in patients with a rising serum CEA level but negative findings for computed tomographic (CT) scans of the abdomen and pelvis, chest radiograph, and colonoscopy or barium enema. Twenty patients with a history of completely resected CEA-producing adenocarcinoma (18 with colon cancer, one with breast cancer, and one with Hodgkin's disease) and a rising serum CEA level were given an intravenous infusion of 2 mg of 111In-labeled ZCE-025 mixed with 38 mg of unlabeled ZCE-025. Planar and single-photon emission CT (SPECT) scans were acquired at 72 and 144 hours, and in 19 of the 20 patients these were positive. Of those 19, 13 underwent exploratory surgery, and cancer was found in 10, and two had a diagnostic biopsy, which confirmed cancer. Three patients who had negative laparotomies and all four patients who did not undergo surgery or biopsy were followed radiologically. In all seven, cancer was subsequently detected at the sites suggested by the ZCE-025 scan. Thus, tumor was confirmed in all 19 patients with positive scans. Five of 13 patients who were explored benefited from the study and the exploratory laparotomy, as disease was entirely resected in four or was subjected to definitive radiation therapy to the pelvis in the fifth. In two additional patients who were not explored, MoAb imaging resulted in definitive therapy to regionally confined recurrent disease. 111In-labeled anti-CEA MoAb ZCE-025 scanning in patients with rising CEA successfully imaged metastatic colorectal cancer that eluded detection by other methods and affected the care given to some. These results suggest an important role for 111In-labeled ZCE-025 scanning among patients with rising CEA and otherwise occult metastatic cancer.

Novel radiolabeled antibody conjugates

“…In contrast, an 111 In-labeled antibody to colorectal cancer had excessive amounts of 111 In in the liver that frequently masked tumor targeting (Abdel-Nabi et al, 1987, 1990Lamki et al, 1990;Patt et al, 1990). In contrast to the monovalent chelateradiometal complex, Le Doussal et al (1989) found that a bivalent structure would be bound more stably at the tumor site, presumably because the divalent hapten-peptide could be crosslinked by two adjacent bsMAbs (Figure 2).…”

Understanding the in vivo fate of radioimmunoconjugates for nuclear imaging

“…Indeed, there are 4 different radioisotopes of iodine that can be used for nuclear imaging and therapy. Specifically, 123 I and 125 I are gamma emitters suitable for SPECT imaging, 124 I is a positronemitting isotope used for PET imaging, and 131 I emits both β and γ rays and can thus be harnessed for both SPECT and radioimmunotherapy. Traditionally, the radioiodination of antibodies has been performed via the direct electrophilic radioiodination of tyrosine residues within the antibody to create radioiodotyrosines.…”

“…120 However, the pre-or coinjection of unlabeled antibodies alongside 111 In-labeled mAbs has proven beneficial in other cases in which the target antigen is not shed. [121][122][123][124] In a different approach, Studer et al introduced a tetrapeptide linker (Ala-Leu-Ala-Leu) between the antibody and the chelator to promote the specific cleavage of the 111 In-chelator complex in the liver. 125 However, this approach led to very limited-if any-improvements in the activity concentrations retained in the liver of mice.…”

Radionuclide-Based Cancer Imaging Targeting the Carcinoembryonic Antigen

“…For example, 111 In-labeled ZCE-025 (an anti-CEA mAb that does not react with normal granulocyte glycoproteins) was investigated in several studies for the detection of primary, metastatic, or recurrent colorectal carcinomas (Abdel-Nabi et al 1988; Abdel-Nabi et al 1991; Kramer et al 1988; Patt et al 1988; Patt et al 1990). Imaging in patients with rising CEA levels successfully detected metastatic colorectal cancer that could not be detected by other methods, therefore changing patient management in many cases.…”