Imaging and dosimetry determinations using radiolabeled antibodies.
Numerous studies using radiolabeled antibodies for imaging and therapy of lymphoma have been reported (Table 4). The targeting of lymphoma associated antigens with MoAb appears to be more favorable than the targeting of antigens on epithelial tumor. Antigen abundance may not be the overriding factor in this favorable targeting, since the number of antigenic sites per cell are often in the same range or lower than those targeted in epithelial tumors. This improved targeting is likely related to the greater access of antibody to the target antigen in lymph nodes, bone marrow, circulation, and other sites. With certain antibodies, trafficking of the cells targeted with the radiolabeled antibody may also result in favorable localization [19]. While the most frequently used isotope for imaging and therapy has been 131I, certain limitations have been observed, including its high-energy gamma rays and resulting lower resolution, and the frequent occurrence of dehalogenation [21,25,98]. Many of the antigens expressed by lymphomas undergo antigenic modulation. Antigens that undergo modulation may be targeted successfully, but once modulation occurs the antibody is broken down and the iodine is rapidly excreted from the cells. While this rapid release from normal organs is an advantage, it is an undesirable event at the tumor site. In contrast to the case of 131I MoAb, modulation may be an advantage for targeting with 111In labeled antibodies, since the radioactive metals are retained for longer periods at the tumor sites; even if the antibody is broken down, the 111In is not easily excreted from the cells [52]. Among the most consistent and favorable targeting observed to date is that seen with 111In T101 in CTCL. These studies have shown concentration of 111In in tumor of 10-100 times that seen in other tumor systems using iodinated antibodies. Unfortunately no studies have followed this lead and performed the necessary comparisons between 111In and 131I MoAb to determine if this is a consistent finding. The use of 99mTc labeled MoAb for imaging lymphomas is in its infancy, although preliminary reports appear promising [71]. While in epithelial tumors preferential tumor targeting may take more than 48 hours in lymphomas, targeting is usually seen within the first 24 hours, which is within the window of imaging time for 99mTc. Therefore, further evaluation of 99mTc antibodies should be performed. Determination of the optimum dose of antibody for imaging has been attempted. Studies using various anti-lymphoma directed antibodies have shown widely varying biodistribution and variable dose-response curves.(ABSTRACT TRUNCATED AT 400 WORDS)
Carrasquillo
J
J
Department of Health & Human Services, National Institutes of Health, Bethesda, MD 20892.
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000097:blood; D000911:Antibodies, Monoclonal / Q000276:immunology; D006689:Hodgkin Disease / Q000000981:diagnostic imaging; D006801:Humans; D007938:Leukemia / Q000000981:diagnostic imaging*; D008223:Lymphoma / Q000000981:diagnostic imaging*; D011829:Radiation Dosage; D016719:Radioimmunodetection
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal