Andrological Disorders in Hematology

Carcinoembryonic Antigen as a Target Cancer Antigen for Radiolabeled Antibodies: Prospects for Cancer Imaging and Therapy

“…It was previously thought that its short half-life of 6 h would preclude anti body imaging, since tumor targeting by anti body may not be accomplished within 24 h [44]. However, this is not true for IgG frag ments, which can show tumor targeting and clearance from normal tissues within a few hours [3,45]. Although conjugation of 99mTc to whole IgG has permitted tumor imaging at 24 h [46], earlier imaging can be accom plished with the use of Fab', for example with 64 Goldenberg CEA as a Target Antigen for RAID and RAIT in 4 h [3,41,[47][48][49].…”

“…Despite the prob lems inherent with dual-isotope subtraction, especially where obvious differences in biodis tribution of the two isotopes are not accom modated, many reports confirmed that prima ry and secondary cancers could be imaged suc cessfully with various radiolabeled anti-CEA antibodies, including polyclonal and mono clonal antibodies (MAbs) with l3lI, l231 ,11'In, or 99mTc labels [reviewed in ref. 3,4,[23][24][25][26][27][28]. A number of these earlier studies also suggested that the use of antibody fragments could alle 63 viate the need for dual-isotope subtraction or other image enhancement methods, since more rapid clearance of background nontargeted tissue and blood occurred than when unmodified IgGs were used [29][30][31].…”

“…Although conjugation of 99mTc to whole IgG has permitted tumor imaging at 24 h [46], earlier imaging can be accom plished with the use of Fab', for example with 64 Goldenberg CEA as a Target Antigen for RAID and RAIT in 4 h [3,41,[47][48][49]. Using a recently devel oped simple and direct Fab' labeling kit for 99mTc [50,51], we and others have demon strated that very small colorectal tumors, in cluding those in the liver, can show 'hot' or rimmed images within a few hours of injection of the radiolabeled agent [3,41,[47][48][49]52], A multicenter trial of this imaging kit in colorec tal cancer patients showed that tumors as small as 0.5-1.0 cm could be disclosed, that the kit is safe (rarely evoking HAMAs after a single application), and is particularly effective in detecting tumors in the liver [53,54]. In pa tients with at least one known site of colorectal cancer, CEA-RAID showed comparable imag ing of liver metastases and somewhat better imaging statistics in the extrahepatic abdomen and pelvis, compared to conventional imaging methods, particularly computed tomography (CT) [53,54].…”

“…A number of MAbs against CEA have been developed and evaluated clinically for tumor targeting. These have been shown to react with different CEA epitopes [3,4,[32][33][34], and those present on circulating blood cells or normal tissues have been shown to be unsuitable for RAID [35,36], The CEA-specific epitope class [32] appears to be the pre ferred target for CEA MAbs [36]. Some studies have attempted mixing two CEA MAbs, but there is little evidence that any combination is superior to the best single CEA MAb agent [37] , Regardless of which CEA MAb has been tried, the overall imaging results have been generally good if the appropriate label and image processing are used.…”

“…a target for radiolabeled antibodies used suc cessfully in cancer imaging, or radioimmu nodetection (RAID), in patients [2], thus pav ing the way for the development of a number of antibody-based cancer imaging and thera peutic agents [3,4], This paper reviews the development, current status, and future per spectives of cancer imaging and therapy with radioactive CEA antibodies. Critical to this development has been a better understanding of the family of CEA molecules and their dif ferent antibody sepcificities, an area which was first provoked by the early description by von Kleist et al [5] of nonspecific cross-react ing antigen (NCA), and advanced by her and her associates over many decades [6].…”