title: Localization of fluorine-18-labeled Mel-14 monoclonal antibody F(ab')2 fragment in a subcutaneous xenograft model.
abstract: 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 micrograms 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 10(8) M-1; 125I, 6.7 x 10(8) 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.
authors.affiliation: Department of Radiology, Duke University Medical Center, Durham, North Carolina 27710.
authors.forename: P K
authors.initials: PK
authors.lastname: Garg
authors.forename: S
authors.initials: S
authors.lastname: Garg
authors.forename: D D
authors.initials: DD
authors.lastname: Bigner
authors.forename: M R
authors.initials: MR
authors.lastname: Zalutsky
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D005462:Fluorine Radioisotopes; D005910:Glioma / Q000378:metabolism; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D016201:Receptors, Lymphocyte Homing / Q000378:metabolism*; D014055:Tomography, Emission-Computed / Q000379:methods*; D014183:Transplantation, Heterologous
chemical_list: D000911:Antibodies, Monoclonal; D005462:Fluorine Radioisotopes; D007140:Immunoglobulin Fab Fragments; D016201:Receptors, Lymphocyte Homing