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At the present time, more than seventy-five
percent of routine nuclear medicine diagnostic procedures use technetium-99m
(99mTc). This isotope is an ideal imaging agent
in that it decays with a half-life of 6.03 hours to 99Tc
primarily by the emission of a 140 KeV gamma-ray. The gamma-ray is high enough in energy to readily penetrate
(escape) tissue but low enough in energy to be absorbed with very
high efficiency by the thin thallium-doped, sodium iodide, single-crystal
slabs used in the various nuclear medicine imaging cameras. Although, other radioisotope generator systems offer some real
advantages over the 99Mo-99mTc generator, the
use of 99mTc is still increasing. Much of the chemistry of 99mTc
in radiopharmaceuticals remains unknown. Technetium is a second-row
transition metal and can assume any oxidation state from +7 to 0. It resembles manganese to a limited
extent and rhenium to a much greater extent. In its compounds, it exhibits coordination numbers from 4 to
9 and their crystal structures show great variety. Complexities in the
chemistry, especially in aqueous solution, make it difficult to assign an
overall role to its behavior in medically useful radiopharmaceuticals as one might
do in the case of much better understood elements like nickel and cobalt.
Compounding this complexity, 99mTc is available at tracer levels,
which does not permit the characterization of its compounds by routine
spectroscopic and analytical methods. Hence, studies are performed by using
either the long-lived radionuclide 99gTc (t1/2= 2.1 x 105
years) or its stable congener, rhenium. In many cases though, different
products are formed at the macroscopic (99gTc or Re) and tracer (99mTc)
levels, primarily due to the different reaction conditions (metal: ligand
ratio, solvent etc), in addition to the fact that many of technetium compounds
in water hydrolyze, polymerize or form colloids. The physical structure of the three most widely utilized 99mTc radiopharmaceuticals are not known: 99mTc Pentetate (99mTc DTPA) used for kidney and brain imaging and assessment of renal perfusion; 99mTc Medronate used as a bone imaging agent to delineate areas of altered osteogenesis; and 99mTc Sodium Phosphates used both for bone and myocardial imaging and blood pool and gastrointestinal imaging. This is problematic, as the FDA now requires structural information prior to the approval for general usage of new pharmaceutical compounds. This work was initiated to try to develop a methodology that satisfies the FDA requirements for these types of radiopharmaceuticals. This project is a collaborative effort between myself, Sylvia Jurisson and J. David Robertson at the University of Missouri, Columbia. We have successfully measured the X-ray absorption spectrum from a solution containing 78 ng of Tc-DTPA. We estimate that the signal to noise ratio can be improved by a factor of 10 and will be useful for the determination of local atomic structure. |
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The Tc K-edge X-ray Absorption spectrum from 78
ng of Tc-DTPA collected in approximately 2 hours at MR-CAT's undulator beamline. |