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Localization of Fluorine-18-labeled Mel-14 Monoclonal Antibody F(ab')₂ Fragment in a Subcutaneous Xenograft Model¹

Departments of Radiology [P. K. G., S. G., M. R. Z.] and Pathology [D. D. B., M. R. Z.] and the Preuss Laboratory for Brain Tumor Research [D. D. B.], Duke University Medical Center, Durham, North Carolina 27710

Positron emission tomography is an imaging method that might improve the effectiveness of radioimmunoscintigraphy and might provide more accurate estimates of monoclonal antibody dosimetry prior to therapy. Because of its widespread availability, 2-h half-life ¹⁸F could be a useful nuclide for labeling monoclonal antibody fragments, provided that adequate tumor uptake and satisfactory tumor:normal tissue ratios could be achieved rapidly. In this study, the tissue distribution of ¹⁸F-labeled Mel-14 F(ab')₂, a monoclonal antibody reactive with gliomas, was evaluated in a s.c. athymic mouse human glioma xenograft model. ¹⁸F labeling was performed using N-succinimidyl-8-(4'-[¹⁸F]fluorobenzylamino)suberate. For paired-label comparisons both in vitro and in vivo, Mel-14 F(ab')₂ was also labeled using N-succinimidyl 3- [¹²⁵I]-iodobenzoate. When 100–120 µg of disuccinimidyl suberate was used in the ¹⁸F-labeled acylation agent synthesis, the binding of ¹⁸F-labeled Mel-14 F(ab')₂ to glioma homogenates was comparable to that of the radioiodinated fragment. Scatchard analyses indicated nearly identical affinity constants for fragments with both labels (¹⁸F, 6.4 x 10⁸ M^-1; ¹²⁵I, 6.7 x 10⁸ M^-1). Tumor levels of ¹⁸F increased between 1 and 2 h and then were relatively constant between 2 and 6 h. When lower levels of disuccinimidyl suberate were used, there was an excellent correlation between ¹⁸F and ¹²⁵I tumor uptake (r = 0.984, slope 1.03–1.04). At 4 h, tumor:normal tissue ratios for ¹⁸F-labeled Mel-14 F(ab')₂ in liver, spleen, muscle, and brain were 2.3, 4.2, 14, and 40, respectively. Localization indices, determined by comparison with ¹⁸F-labeled nonspecific F(ab')₂, were 3.7 at 4 h and 6.9 at 6 h for tumor and about 1 for normal tissues, indicating the specificity of ¹⁸F-labeled Mel-14 F(ab')₂ tumor uptake.

¹ This work was supported by Department of Energy Grant DE-FG05-89ER-60789 and NIH Grants CA 42324, CA 11898, CA 56115, and NS 20023.

² To whom requests for reprints should be addressed, at Department of Radiology, Box 3808, Duke University Medical Center, Durham, NC 27710.

Received 4/ 1/92. Accepted 7/ 9/92.

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