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Directly and Indirectly Technetium-99m-Labeled Antibodies A—Comparison of In Vitro and Animal In Vivo Properties

Departments of Nuclear Medicine and Medicine, University of Massachusetts Medical Center, Worcester, Massachusetts

Correspondence: For correspondence and reprints contact: D. J. Hnatowich, Dept. Nuclear Medicine, University of Massachusetts Medical Center, Worcester, MA 01655.

ABSTRACT

To investigate the in vivo and in vitro properties of ^99mTc when labeled to antibodies via one direct and one indirect method, the B72.3 and C110 IgG antibodies were radiolabeled directly via stannous ion reduction and indirectly via the hydrazino nicotinamide chelator and compared in vitro and in vivo. Antibody avidity (but not immunoreactive fraction) appeared to be independent of labeling methods for both antibodies. Following stannous ion reduction, antibodies were fragmented by denaturing SDS PAGE although only slight evidence of fragmentation was found in vivo. The direct label was instable to transchelation to cysteine and glutathione in vitro and in vivo. Following intravenous administration, urinary excretion of activity was threefold greater for the direct label and was almost exclusively labeled cysteine and glutathione. Significant differences in the biodistribution of ^99mTc were also observed: liver levels were lower, kidney levels were higher and clearance of label from blood and tissues was faster for the direct label. At Day 1, tumor accumulation was threefold lower for the direct label although most normal tissues were also lower. In conclusion, when labeled to two antibodies by one direct method, ^99mTc is unstable towards transchelation relative to one indirect method. These relative instabilities greatly influenced the biodistributions in mice and may influence the quality of images obtained in patients.

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