| Abstract: |
Background. Colon‐specific antigen‐p is a tumor‐associated antigen present in approximately 60% of colorectal cancers. Preclinical studies have shown that the murine monoclonal antibody Mu‐9 has excellent tumor‐targeting abilities; therefore, clinical studies were initiated. Methods. The immunoglobulin G and F(ab′)2 were radiolabeled with 131I and administered to 13 and 12 patients, respectively, with advanced gastrointestinal cancer (colon, rectal, and pancreatic) for radioimmuno‐detection or radioimmunotherapy. Results. Even in patients with highly elevated carcinoembryonic antigen levels, only one patient showed appreciable complexation of the labeled antibody, suggesting the epitope may not be highly expressed in the blood. Fifty percent of 131I‐Mu‐9 immunoglobulin G was cleared from the blood within 41 ± 13 hours, while it took only 19 ± 8 hours for the same amount of 131I‐F(ab′)2 to be cleared from the blood. Lesion detection in the abdomen, liver, and pelvis was greater than 90% for either the immunoglobulin G or F(ab′)2. The dose absorbed by the normal organs, except the kidneys, was two‐ to threefold less for the F(ab′)2 than for the whole immunoglobulin G. The dose to the kidneys was similar for both forms of immunoglobulin. The average tumor dose for 131I‐Mu‐9 immunoglobulin G was 13.9 ± 11.0 cGy/mCi, and for 131I‐F(ab′)2 was 4.9 ± 2.9. Tumor/red marrow dose ratios for the whole immunoglobulin G were 4.3 ± 3.0, compared to 3.3 ± 1.9 for the F(ab′)2, suggesting the therapeutic window for the two forms of immunoglobulin may be similar. Eight of nine patients given the whole immunoglobulin G developed highly elevated levels of human anti‐mouse antibody, whereas lower values were observed in five of seven patients given the F(ab′)2. Conclusions. These initial results support the need for further evaluation of Mu‐9 immunoglobulin G and F(ab′)2 for targeting gastrointestinal cancer for radioimmunotherapy. Cancer 1994; 73:864–77. Copyright © 1994 American Cancer Society |
| Keywords: |
adult; clinical article; aged; unclassified drug; clinical feature; clinical trial; conference paper; pancreas cancer; animal; mice; tumor localization; computer assisted tomography; radiotherapy dosage; tumor markers, biological; gastrointestinal neoplasms; antibodies, monoclonal; antigens, neoplasm; immunoglobulin g; drug distribution; tissue distribution; iodine radioisotopes; dosimetry; colon cancer; drug infusion; drug clearance; phase 1 clinical trial; drug half life; radioimmunotherapy; rectum cancer; antibody formation; half-life; scintigraphy; drug elimination; middle age; radioimmunodetection; gastrointestinal carcinoma; immunoglobulin f(ab')2 fragment; human; male; female; priority journal; support, u.s. gov't, p.h.s.; monoclonal antibody i 131; immunoglobulins, fab; antibody targeting; clinical studies; colon cancer antigen; external scintigraphy; radiolabeled monoclonal antibody, colorectal cancer; monoclonal antibody mu 9
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