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Pharmacokinetics of ^99mTc-Metallothionein-B72.3 and Its F(ab')₂ Fragment¹

Medical Products Department, Immunopharmaceutical Research and Development, E. I. duPont de Nemours and Company, Inc., North Billerica, Massachusetts 01862

The radionuclide of choice for use in diagnosis in most nuclear medicine diagnostic procedures is ^99mTc. It is important, therefore, to establish whether there is potential clinical efficacy of an antitumor antigen directed monoclonal antibody labeled with ^99mTc. We have investigated the potential use of a ^99mTc labeled antibody complex which uses conjugation of the metal binding protein, metallothionein (MT), to bind the radiolabel. The stability and pharmacokinetics of the conjugates in normal and tumor bearing mice were compared to radioiodinated controls. Measurements done in CD-1 mice comparing either ^99mTc-MT-B72.3 with ¹²⁵I-B72.3 or ^99mTc-MT-F(ab')₂ with ¹²⁵I-F(ab')₂ indicated that the ^99mTc-MT-B72.3 cleared at a rate which was faster than ¹²⁵I-B72.3 while the two radiolabeled F(ab')₂ fragments cleared at similar rates. The ^99mTc from both labeled IgG and F(ab')₂ was found in the kidneys and urine. While all the ^99mTc in the urine was in the form of low molecular weight compounds, the serum contained radioactivity comigrating on size exclusion chromatography with the injected monoclonal antibody. With the exception of kidneys, organ values for ^99mTc-MT-B72.3 were consistently lower than the ¹²⁵I values, while the ^99mTc-MT-F(ab')₂ cleared other organs at similar rates to those for the iodinated monoclonal antibody. Both ^99mTc-MT-B72.3 and F(ab')₂ showed higher 24-h tumor:blood ratios than the iodinated proteins. Due to the pharmacokinetic properties of ^99mTc-MT-F(ab')₂ and the half-life of ^99mTc, ^99mTc-MT-F(ab')₂ is the agent best suited for imaging.