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Fluorine-18-Labeled Monoclonal Antibody Fragments: A Potential Approach for Combining Radioimmunoscintigraphy and Positron Emission Tomography

Departments of Radiology and Pathology and the Preuss Laboratory for Brain Tumor Research, Duke University Medical Center, Durham, North Carolina

Correspondence: For reprints contact: Michael R. Zalutsky, PhD, Duke University Medical Center, Department of Radiology, Box 3808, Durham, NC 27710.

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-succinimidlyl-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-[¹²⁵l]iodobenzoate {¹⁸F, affinity constant = (6.7 ± 1.1) x 10⁸ M^–1; ¹²⁵I, affinity constant = (8.8 ± 0.6) x 10⁸ 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.

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