Ytterbium-169 Diethylenetriaminepentaacetic Acid Complex

RADIOACTIVE mercury-labeled chlormerodrin is the most widely used brain scanning agent today, but technetium-99m pertechnetate is continually gaining popularity and may soon replace it. Short-lived indium-113m chelate has also been employed successfully for brain (11) and kidney (9) scanning. These short-lived isotopes have greatly improved radionuclide imaging with decreased irradiation of the patient. We have developed a new radiopharmaceutical which depends on a short biological half-life to limit the radiation dose. This compound is prepared by chelating trivalent ytterbium 169, an isotope of one of the rare earth elements, with diethylenetriaminepentaacetic acid (DTPA). Ytterbium has several stable isotopes. The stable 168Yb has a natural abundance of only 0.135 per cent, but a very high thermal neutron capture cross-section (11,000 barns). It is available in enriched form, facilitating the production of 169Yb of high specific activity (greater than 100 mCi/mg). The product contains less than 1 per cent of 175Yb, which emits beta and gamma rays and decays with four and two-tenths days physical half-life. Ytterbium 169 has a physical half-life of thirty-two days and emits primarily gamma rays (8-308 keV). The predominant energies of the gamma rays are 63 and 198 keV, which are suitable for external radiation detection such as scanning. Ytterbium, like other lanthanons, is largely accumulated in the bones and the liver (3), but, when chelated with DTPA, it is excreted in the urine. Preparation of Radiopharmaceutical Ytterbium 169 was obtained as YbCl3 in HC1 from the 3M Company, St. Paul, Minn. The specific activity ranged from 20 to 100 mCi/mg. Ten mCi of 169Yb was diluted to 5 ml with 0.05 N HC1; then 10 mg of DTPA in 5 ml of pyrogen-free water was added, after which the pH was adjusted to between 6.5 and 7 with 0.5 N and 0.05 N NaOH solutions. Sodium chloride (60 mg) was added to make the solution isotonic. It was then sterilized by autoclaving at 15 psi for twenty minutes. The whole-body retention of the radioactivity (excluding the tail) was measured forty-eight hours after an intravenous injection of 169Yb-DTPA complex into the tail vein of white mice. The effects of storage, pH, excess DTPA, and carrier elements were studied to develop a preparation which would have minimum retention in the body. The final product was stable after repeated autoclaving and after storage for several months. There was no significant difference in the whole-body retention of the complex when the final pH was varied between 5 and 8. Studies with varying amounts of DTPA indicated that the molar excess of DTPA for maximum chelation depended on the amount of ytterbium. With higher amounts of 169Yb, a 3–10 molar excess of DTPA was sufficient to achieve maximum binding.