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Adams GP, McCartney JE, Wolf EJ, Eisenberg J, Huston JS, Bookman MA, Moldofsky P, Stafford WF, Houston LL, Weiner LM
Enhanced Tumor Specificity of 741f8-1(Sfv')(2), an Anti-C-Erbb- 2 Single-Chain Fv Dimer, Mediated by Stable Radioiodine Conjugation
Journal of Nuclear Medicine (1995) 36:2276-2281.
Abstract
The goal of this study was to determine if the stabilization of the radioiodine-protein bond by the N-succinimidyl p- iodobenzoate (PIB) method 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 murine model. Methods: Gamma camera images were acquired 21 hr after intravenous administration of I-131-741F8-1 (SFv')(2) labeled by the p- iodobenzoate or chloramine T methods. The stability of the radioiodine-protein bond also was assessed in plasma samples after intravenous injection of I-125-741F8-1 (sFv'), labeled by either the chloramine T or p-iodobenzoate methods. Results: By 6 hr postinjection, 97% of the activity associated with the I- 125-741F8-1 (sFv'), labeled by the p-iodobenzoate 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 molecule can significantly increase the degree and specificity of tumor targeting. Significantly greater tumor retention (p < 0.005) and lower blood (p < 0.001), spleen (p < 0.001) and stomach (p < 0.005) retention were observed in biodistribution studies when the p- iodobenzoate conjugate was used. This resulted in superior tumor-to-organ ratios for all tissue samples studied. Conclusion: These observations may have clinical relevance for the use of radiolabeled sFv as imaging agents.
Note
Publication Date: 1995-12-01.
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