title: Fluorine-18-labeled monoclonal antibody fragments: a potential approach for combining radioimmunoscintigraphy and positron emission tomography.
abstract: Monoclonal antibody fragments labeled with 18F could be useful for PET if selective tumor uptake could be achieved within a few half-lives of this nuclide. To evaluate this possibility, the F(ab')2 fragment of Mel-14, an antibody reactive with gliomas and other tumors, was labeled by reaction with N-succinimidyl-4-[18F]fluorobenzoate. The in-vitro binding properties of 18F-labeled Mel-14 F(ab')2 were nearly identical to those observed when this F(ab')2 was labeled by reaction with N-succinimidyl-4-[125I]iodobenzoate (18F, affinity constant = (6.7 +/- 1.1) x 10(8) M-1; 125I, affinity constant = (8.8 +/- 0.6) x 10(8) M-1). The tissue distribution of the two labeled fragments was compared in paired-label studies performed in athymic mice with subcutaneous D-54 MG human glioma xenografts. Uptake of both nuclides in tumor was rapid with levels as high as 18.7% +/- 1.1% injected dose/g for 18F and 19.4% +/- 1.0% injected dose/g for 125I observed by 4 hr after injection. Tumor-to-normal tissue ratios for 18F-labeled Mel-14 F(ab')2 at 4 hr ranged between 0.8:1 for kidneys to 40:1 for brain. These results suggest that it may be feasible to use 18F-labeled antibody fragments for imaging tumors with PET.
authors.affiliation: Department of Radiology, Duke University Medical Center, Durham, North Carolina 27710.
authors.forename: G
authors.initials: G
authors.lastname: Vaidyanathan
authors.forename: D D
authors.initials: DD
authors.lastname: Bigner
authors.forename: M R
authors.initials: MR
authors.lastname: Zalutsky
mesh_terms: D000818:Animals; D005462:Fluorine Radioisotopes; D005910:Glioma / Q000000981:diagnostic imaging* / Q000378:metabolism; D006801:Humans; D007140:Immunoglobulin Fab Fragments; D007553:Isotope Labeling; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D016719:Radioimmunodetection / Q000379:methods*; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed / Q000379:methods*; D014183:Transplantation, Heterologous
chemical_list: D005462:Fluorine Radioisotopes; D007140:Immunoglobulin Fab Fragments