The aim of this study was to investigate targeting of the liver
metastases by directly 99mTc-labeled complete (
IgG) and fragmented
antibodies [F(ab')2 and Fab'] in relation to their kinetics and metabolic fate. A total of 127 patients with metastatic
colorectal cancer were examined [
IgG1, BW 431/26 (Behringwerke, Marburg, Germany) n = 50; F(ab')2, F023C5 (Sorin Biomedica, Saluggia, Italy) n = 58; Fab',
IMMU-4 (Immunomedics, Morris Plains, NJ) n = 19]. Native
monoclonal antibodies (MAbs), serum samples from 10 min to 24 h postinjection (p.i.), and urine were analyzed by gel filtration chromatography. Kinetic data were deduced from whole-body and single-photon emission computed tomographic scans, performed 10 min to 24 h p.i. (region-of-interest technique). In BW 431/26, 96% of injected activity was labeled
IgG1; in F023C5, 29% was F(ab')2, and 71% was Fab'; and in
IMMU-4, 92% was Fab', and 8% was F(ab')2. Serum half-lives were:
IgG1, 36 h (liver uptake predominant); F(ab')2, 16 h; and Fab', 4 h (renal uptake predominant). All MAbs were metabolized, fragments more rapidly than
IgG, to low-molecular-weight products and excreted into the urine (e.g., Tc-
cystine). In targeting liver
metastases, sensitivities were found to be higher for fragments (44.1, 72.5, and 80% for BW 431/26, F023C5, and
IMMU-4, respectively) but at significantly lower
tumor:background ratios than with
IgG (1.78 +/- 0.29 versus 1.29 +/- 0.11 and 1.43 +/- 0.53; P < 0.01). With
IgG, there was a continuous
tumor uptake over 24 h, whereas with fragments, the maximal uptake occurred mostly within 1 h, with subsequent clearance being slower for
antigen-bound activity than for nonspecific background. Hence, diagnosis was possible mostly after 4 h with fragments but often not before 24 h with
IgG. These results show that the higher sensitivity of fragments in liver lesion targeting at earlier p.i. times does not rely on an increased antibody uptake but on a more rapid clearance of nonspecific background activity due to faster metabolism and excretion. Intact MAbs show a slow, continuous uptake, leading to higher
tumor:background ratios at later p.i. times, often beyond the imaging possibilities of 99mTc.