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Pharmacokinetics of 99mTc-metallothionein-B72.3 and its F(ab')2 fragment.

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.