ENHANCED TUMOR SPECIFICITY OF 741F8-1(SFV')(2), AN ANTI-C-ERBB-2 SINGLE-CHAIN FV DIMER, MEDIATED BY STABLE RADIOIODINE CONJUGATION

The goal of this study was to determine if the stabilization of the ra dioiodine-protein bond by the N-succinimidyl p-iodobenzoate (PIB) meth od improved the degree and specificity of tumor localization of I-125- 741F8-1 (SFV')(2), an anti-c-erbB-2 sFv dimer, in an immunodeficient m urine model. Methods: Gamma camera images were acquired 21 hr after in travenous administration of I-131-741F8-1 (SFv')(2) labeled by the p-i odobenzoate or chloramine T methods. The stability of the radioiodine- protein bond also was assessed in plasma samples after intravenous inj ection of I-125-741F8-1 (sFv'), labeled by either the chloramine T or p-iodobenzoate methods. Results: By 6 hr postinjection, 97% of the act ivity associated with the I-125-741F8-1 (sFv'), labeled by the p-iodob enzoate method was protein bound compared with 61% after labeling with the chloramine-T method. These observations indicate that increasing the stability of the conjugation between the radioiodine and the sFv m olecule can significantly increase the degree and specificity of tumor targeting. Significantly greater tumor retention (p < 0.005) and lowe r blood (p < 0.001), spleen (p < 0.001) and stomach (p < 0.005) retent ion were observed in biodistribution studies when the p-iodobenzoate c onjugate was used. This resulted in superior tumor-to-organ ratios for all tissue samples studied. Conclusion: These observations may have c linical relevance for the use of radiolabeled sFv as imaging agents.