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Diagnostic Accuracy and Tumor-targeting Kinetics of Complete versus Fragmented ^99mTc-labeled Anti-Carcinoembryonic Antigen Antibodies: An Intraindividual Comparison¹

Departments of Nuclear Medicine [T. M. B., W. S. B., H. J. B., F. G. W.] and Surgery [M. W. K., J. R. S.], Friedrich-Alexander-University Erlangen-Nuremberg, D-91054 Erlangen, Germany

The goal of this study was to intraindividually compare a complete versus a fragmented, directly ^99mTc-labeled, monoclonal anti-carcinoembryonic antigen (CEA) antibody, with respect to their antigen-targeting kinetics, sensitivity, and diagnostic accuracy in patients with CEA-expressing tumors. Twenty-five patients were investigated with the ^99mTc-labeled anti-CEA IgG1 BW 431/26 and the F(ab')₂/Fab' fragment mixture F023C5 within 7 days. For quantitative analysis, the region of interest technique was applied to planar scans, whole-body scans, and single photon emission computed tomography slices 10 min to 48 h postinjection (PI). Final correlations were performed according to the histopathology after surgery or biopsy. Earliest tumor detection was possible with complete IgG1 4 h PI (52% of finally positive lesions). Twenty-four- or even 48-h scans were necessary in 48% of finally positive lesions; tumor detection with fragments was possible in 17% at 1 h PI and in 94% at 4 h PI. With both monoclonal antibodies, in 35%, single photon emission computed tomography was necessary for tumor detection. Absolute antibody uptake in tumor lesions was higher with complete monoclonal antibodies than with fragments. The sensitivity of fragments was higher in detecting primary tumors, local recurrences, and lymph node metastases. For detection of liver metastases, sensitivity was also higher for fragments than for IgG (87 versus 73%), but in scintigraphically positive lesions, tumor:background ratios were significantly lower with fragments (1.26 ± 0.12 versus 1.70 ± 0.32; P < 0.01). Therefore, fragments seem to be more suitable for earlier detection of lesions known for their good vascularization, vascular permeability, and antigen accessibility, such as local recurrences, lymph node metastases, and peritoneal carcinomatoses. In liver metastases (high interstitial pressure, low vascular leakage), sensitivity of fragments is higher, but their rapid serum and whole-body clearance lead to a lower absolute antibody uptake, with the consequence of significantly lower tumor:background ratios than with IgG.