Article: Eckelman WC. Unparalleled contribution of Technetium-99m to medicine over 5 decades. JACC Cardiovasc Imaging 2009; 2: 364–368.
Summary prepared by Aqib Momin for discussion on 10-24-17:
The study of radioactivity and its accompanying risks and potential uses is overall a fairly new science. Of course, the early pioneers of this field include names such as Wilhelm Roentgen, Henri Becquerel, and the Curies. Eckelman’s article, however, starts off by first abridging the history of radioactive materials as they have been used in medicine, an undertaking that is less than a century young. Indeed, nuclear medicine has its roots in a study conducted by George C. de Hevesy in 1923 using Lead-212 as a biological tracer. Since then, landmark studies involving iodine radioisotopes have found great success. Eckelman attributes the success of Iodine-131 to its high availability and conversion properties. Despite this, Eckelman states that the real growth in nuclear medicine arose from the discoveries of Molybdenum-99 (Mo-99) and Technetium-99 (Tc-99m), with Tc-99 becoming a standard in 85% of radio-imaging diagnostics.
The origin of this infamous “instant-kit” conversion between Mo-99 and Tc-99 is then covered in great detail. While it was known at the time that there was an unknown element after Molybdenum and above Rhenium, it was not until an irradiated Molybdenum cyclotron deflector had been analyzed was that element found. Emilio Segre of University of California Berkeley, Carlo Perrier of University of Palermo, and Glenn Seaborg are credited with this discovery. The Brookhaven National Laboratory (BNL) in Upton, NY then made great strides to bring Tc-99m into the medical field by first discovering the ease at which Tc-99m could be leached from Mo-99 absorbed into alumina. Jim Richards of BNL then illustrated Tc-99m’s superior imaging properties with the Anger camera, finding 50% absorption in 4.6cm of tissue at low energies. The author, Eckelman himself, describes his journey in becoming involved with ongoing work at BNL to expand the utility of Tc-99m. Together, they found a convenient way using stannous ions to reduce Tc-99m to a lower oxidation state, which in turn greatly enhanced its affinity for chelating agents and biological molecules (e.g. RBCs).
Eckelman’s personal developments into furthering the use of Tc-99m continued at the George Washington University (GWU) and at the Squibb Institute for Medical Research. At GWU, Eckelman realized the struggles of retaining biological function on radiolabeled molecules. While several attempts had failed, including radiolabeled palmitic acid, there were a small number of Tc-99m labeled molecules that retained their biological activity such as TRODAT, a marker for measuring dopamine transporter densities. At Squibb, Eckelman served as the VP for Diagnostics and one of his ventures had been testing the myocardial perfusion abilities of TC-99m-labeled teboroxime. He recalls being limited by technology as the SPECT machines of the time were not fast enough to measure teboroxime perfusion. This serves as an important reminder of the close correlation between imaging devices and radiopharmacy, given that SPECT machines are finally reaching such capabilities in the current day.
We can argue that the future of Tc-99m lays in continuing to act as a radiotracer, namely in peptides. Eckelman says one of the strengths of Tc-99m is that the chelate does not affect peptide biological activity when appropriately placed and several peptides have held up to this test including somatostatin, neurotensin, and opioids. However, the future of Mo-99/Tc-99m production is also in question. While the generators and instant kits of the 50’s and 60’s made it possible for Tc-99m studies to flourish so much, will the bulky method of producing Mo-99 from reactors be replaced by other methods? Eckelman hypothesizes that Tc-99m may start being shipped as either pertechnetate or in ready-to-go form. He also notes that I-123 use may expand as imaging moves toward smaller and smaller molecules. However, Eckelman ends on the note that it is impossible to predict the future and generation of Tc-99m as almost all products, great as they may have been in their prime, have been cannibalized at some point. It will be worth watching if the ever-useful Tc-99m radiopharmaceuticals continue to stand the test of time.