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Human serum albumin has been conjugated to 1-(p-benzenediazonium)(ethylenedinitrilo)tetraacetic acid, a powerful chelating agent, and radioactive "'1indium ions have been added specifically to the chelating groups. The product, with a specific radioactivity of about 1 mCi/mg of protein, was employed as a radiotracer in scintillation scanning studies with human volunteers. Results show that 48 hr after injection, practically all of the label remains attached to albumin. This is confirmed by electrophoresis of serum proteins; 7 days after injection, 85% of the radioactivity in the serum is still in the albumin fraction. These observations agree with in vitro studies of the labeled albumin in human serum, where loss of the metal ion from the chelating group to the protein transferrin amounts to less than 3% after 1 week and less than 5% after 2 weeks. A metal ion may be attached to a biological molecule by means of a "bifunctional" chelating agent capable of forming a covalent bond to the desired molecule. The conjugation of a derivative of EDTA to a large molecule permits the addition of any of a number of metal ions to form a stable chelate. In principle, this can lead to the utilization of the physical properties of various metal ions in a broad range of applications. Of particular importance is the tagging of certain biological molecules with short-lived radionuclides, and the use of these tagged molecules in medical diagnosis (1).A case in point is the use of chelates containing radioisotopes of indium for tracer studies. The intravenous injection of such compounds into human patients often leads to the binding of a large fraction of the radioactive metal by the serum protein transferrin, with the result that the observed behavior of the radionuclide is characteristic of the transferrin-indium complex (2, 3). The rapid action of apo-transferrin in removing trivalent iron from chelates is also well known (4, 5). Before biomolecules labeled with indium chelates can be considered valid radioindicators in vivo, it must be shown that the chelates are thermodynamically stable or kinetically inert to the extent that loss of indium is negligible.Previously, we have studied the metabolism of proteins conjugated with indium chelates by measuring the biological lifetime of the label in mice and by observing the distribution of radioactivity among, serum proteins in rabbits (1, 6). The results of these studies suggested that the protein-chelate conjugates were reasonably stable in vivo, but that as much as 50% of the metal ion might eventually become bound to transferrin and be sequestered in the liver and bone marrow. The present studies were undertaken to provide a detailed account of the behavior of carrier-free amounts of the albumin-chelate conjugate, both in vivo and under physiological conditions in vitro. MATERIALS AND METHODSAll reagents were the purest commercially available products, used without further purification except where noted. Chromatographic columns and materials were obtained from BioRad Lab...

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The residue and extraction of technetium-labelled methylene diphosphonate (99mTc-MDP), a substance used in bone scanning, was examined in the canine tibia and found to be low. Examination of washout curves suggested that there were four compartments in cortical bone, a vascular, a perivascular, a bone fluid and a bone compartment. After an osteotomy in the canine tibia the residue of 99mTc-MDP increased. This was believed to be due to an increase in the blood supply to the bone and to an associated increase in new bone available for exchange. Bone scanning in a fracture is therefore a reflection of the vascular status of the bone being examined and of the uptake by bone. This is dependent on there being an adequate blood supply to the bone and an increased number of mineral-binding sites.

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