A comparative study of Co-57 labeled 4-ICE and 4-BACE immunoconjugates: Effect of conjugation method and antibody/tumor model system on biodistribution
- Brookhaven National Lab., Upton, NY (United States); and others
Previously we have shown that radioimmunoconjugates of semi-rigid 4-isothiocyanato- and 4-bromoacetamido-cyclohexyl EDTA (4-ICE and 4-BACE) are more stable in vivo than those prepared using DTPA dianhydride. Here we report the effect of MAb/tumor model system on the biodistribution of Co-57 labeled 4-ICE and 4-BACE immunoconjugates in human tumor xenografted nude mice. Three model systems (MAb/tumor cells) were investigated: BR 15-6A F(ab{prime}){sub 2}/SW 948 cells (system I), anti-CEA F(ab{prime}){sub 2}/LS 174T cells (system II), and 17-1A lgG/SW 948 cells (system III). Labeling yields were 92-95% (4-ICE) and 30-50% (4-BACE), serum stability at 4d was 90-95%, and immunoreactivity retention was 80 {plus_minus}10%. In system I, both ligands gave similar uptakes (%1D/g at 24 and 96h resp.) into tumor (T,8.5 and 1), blood (B,3.5 and 0.25), liver (L,5 and 1.5), and bone (BO, 1.2 and 0.3). However, the kidney (K) uptake and whole body retention (WBR, % ID) were higher for 4-lCE than for 4-BACE. In system II, 4-ICE gave higher T uptake (20.6 and 12.5) than 4-BACE (14.8 and 8.9), but similar WBR and uptake into other tissues. In system III, 4-BACE gave higher T (14.6 and 17.1) and B(17.4 and 8.2) uptakes than 4-ICE(13.5 and 3.1, and 13.4 and 0.74 resp.). The WBR, however, was higher at 24h (97%) and lower at 96h (30%) for 4-ICE than for 4-BACE (90% and 65% resp.). Uptakes in other tissues were similar. The overall trend in terms of absolute tumor uptake and tumor to normal tissue ratios was: anti-CEA F(ab{prime})2/LS174T > 17-1A lgG/SW948 > BR 15-6A F(ab{prime})2/SW948. These results demonstrate that the in vivo distribution of seemingly analogous radioimmunoconjugates varies depending on the model system used for evaluation, and that the method of ligand-MAb conjugation (thiourea vs amine-amide linkage) can also produce differences in biodistribution.
- Research Organization:
- Brookhaven National Laboratory (BNL), Upton, NY
- DOE Contract Number:
- AC02-76CH00016
- OSTI ID:
- 200378
- Report Number(s):
- CONF-940605--
- Journal Information:
- Journal of Nuclear Medicine, Journal Name: Journal of Nuclear Medicine Journal Issue: Suppl.5 Vol. 35; ISSN JNMEAQ; ISSN 0161-5505
- Country of Publication:
- United States
- Language:
- English
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