Medicine radiotracers

Acknowledging the important part that 99mTc(V) radiopharmaceuticals are playing in nuclear medicine, advances in their coordination chemistry, as attained by new syntheses and better structural characterization, are discussed with respect to the design of Tc(V) radiotracers. In the light of current interest in making technetium complexes active in vivo, a chapter considering several aspects of reactivity is included. 

Scintigraphic imaging is a noninvasive imaging technique commonly applied in nuclear medicine. Radiolabeled compounds (called radiopharmaceuticals or radiotracers) are administered intravenously to patients for diagnostic or, in certain cases, therapeutic purposes. The in vivo distribution can provide important physiological information about tissue function. 

Nuclear chemistry consists of a four-pronged endeavor made up of (a) studies of the chemical and physical properties of the heaviest elements where detection of radioactive decay is an essential part of the work, (b) studies of nuclear properties such as structure, reactions, and radioactive decay by people trained as chemists, (c) studies of macroscopic phenomena (such as geochronology or astrophysics) where nuclear processes are intimately involved, and (d) the application of measurement techniques based upon nuclear phenomena (such as nuclear medicine, activation analysis or radiotracers) to study scientific problems in a variety of fields. The principal activity or mainstream of nuclear chemistry involves those activities listed under part (b). 

Today the largest number of applications of radiotracers is in biology and medicine. Because of the large number of applications, it is beyond the scope of this work to review them in any detail. Instead, we shall focus on three specific applications, one that is very old, one that is middle-aged, and one that is adolescent in its scope, if not in its development. We refer to autoradiography, radioimmunoassay, and DNA (deoxyribonucleic acid) analysis, respectively. 

Radiochemistry is defined as the chemical study of radioactive elements, both natural and artificial, and their use in the study of chemical processes (Random House Dictionary, 1984). Operationally, radiochemistry is defined by the activities of radiochemists, that is, (a) nuclear analytical methods, (b) the application of radionuclides in areas outside of chemistry, such as medicine, (c) the physics and chemistry of the radioelements, (d) the physics and chemistry of high-activity-level matter, and (e) radiotracer studies. We have dealt with several of these topics in Chapters 4, 13, 15, and 16. In this chapter, we will discuss the basic principles behind radiochemical techniques and some details of their application. 

To monitor tumor response to capecitabine therapy noninvasively, Zheng and co-workers, from the Indiana University School of Medicine, developed the synthesis of the fluorine- 18-labeled capecitabine as a potential radiotracer for positron emission tomography (PET) imaging of tumors.28 Cytosine (20) was nitrated at the C-5 position with nitric acid in concentrated sulfuric acid at 85°C, followed by neutralization to provide 5-nitrocytosine (27) in moderate yield. This nitro pyrimidine was then carried through the glycosylation and carbamate formation steps, as shown in the Scheme below, to provide the 6/s-protected 5-nitro cytidine 28 in 47% for the three-step process. Precursor 28 was then labeled by nucleophilic substitution with a complex of 18F-labeled potassium fluoride with cryptand Kryptofix 222 in DMSO at 150 °C to provide the fluorine-18-labe led adduct. This intermediate was not isolated, but semi-purified and deprotected with aqueous NaOH in methanol to provide [l8F]-capecitabine in 20-30% radiochemical yield for the 3-mg-scale process. The synthesis time for fluorine-18 labeled capecitabine (including HPLC purification) from end of bombardment to produce KI8F to the final formulation of [18F]-1 for in vivo studies was 60-70 min. 

Applications include the use of radionuclides in geo- and cosmochemistry, dating by nuclear methods, radioanalysis, the use of radiotracers in chemical research, Mossbauer spectrometry and related methods, the use of radionuclides in the life sciences, in particular in medicine, technical and industrial applications and investigations of the behaviour of natural and man-made radionuclides, in particular actinides and fission products, in the environment (geosphere and biosphere). Dosimetry and radiation protection are considered in the last chapter of the book. 

Medical science provides a framework or paradigm in which 10 understand disea.se and to maintain health. Nuclear medicine is the branch of medical science that contributes to medicine by the use of the radiotracer method for diagnosis and use of in vivo unsealed radioactivity for therapy. 

COST Action B3 (1992-1997) was devoted to the development of new radiotracers for nuclear medicine application and methods of quality assurance. National institutions of sixteen European states participated in five Working Groups (WG). 

Srivastava SC, Meinken G, Smith TD, Richards P (1977) Problems associated with stannous " Tc-radiopharmaceuticals. Int J Appl Radiat Isot 28 83-95 Srivastava SC, Richards P (1983) Technetium-labelled compoimds. In Rayudu GVS (ed) Radiotracers for medical apphcations, CRC series in radiotracers in bioliology and medicine. CRC Press, Boca Raton, pp 107-185... 

Hladik WB, III, Ponto JA, Lentle BC, Laven DL (1987b) Iatrogenic alterations in the biodistribution of radiotracers as a result of drug therapy reported instances. In Hladik WB, III, Saha GB, Study KT (eds) Essentials of nuclear medicine science. Williams Wilkins, Baltimore,... 

Btill U, Schicha H, Biersack H-J, Knapp WH, Reiners Chr, Schober O (eds) (1996) Nuk-learmedizin, 2nd edn. Georg Thieme, Stuttgart Colombetti LG (ed) (1976-1986) CRC Series in radiotracers in biology and medicine. CRC Press, Boca Raton ... 

COST is a European cooperation in the field of scientific and technical research. COST Action B3 was devoted to the development of new radiotracers for nuclear medicine application and methods of quality assurance. The main objectives of the cooperation were defined in a preparatory meeting in Vienna on 12 October 1990. Fifteen participants from six member states worked out a draft of the Memorandum of Understanding (MOU), receiving expert advice from the Austrian Ministry of Science and Research. 

Some persons have thought that the increasing emphasis and development of positron-emitting radiotracers in nuclear medicine would result in a decrease in the development and use of single photon-emitting radiotracers. That this is not the case is illustrated hy the fact that there were 302 presentations involving technetium-99m at the June 2006 annual meeting of the Society of Nuclear Medicine in the United States. Iodine-123 accounted for 88 presentations, and indium-111 for 81. 

The uses of radioisotopes in medicine are extremely important. Certain elements are readily absorbed by particular organs in a human body, and this is capitalized upon in the use of radiotracers (introduced by food or drug intake) to probe the function of human organs. An advantage of the technique is that it is non-invasive. 

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