Radiopharmaceuticals labelling

Technetium is usually supplied in the form of heptavalent pertechnetate. Consequently, the syntheses of technetium complexes is necessarily accompanied by the reduction of pertechnetate. When concentrated hydrochloric acid is employed as a reductant, tetrachlorooxotechnetate(V) complexes can easily be obtained. A further reduction procedure is required to obtain hexachlorotech-netate(IV). Using these complexes, a number of technetium complexes have been synthesized by ligand substitution. The importance of preparative substitution reactions also increases in the light of the design and preparation of radiopharmaceuticals labelled with 99mTc and 188Re. 

A specialized application of microwave-assisted organic synthesis involves the preparation of radiopharmaceuticals labeled with short-lived radionuclides, particularly for use in positron emission tomography [70-72]. This represented an excellent application of microwave technology, where the products must be prepared quickly and in high radiochemical yield, on a small scale. 

The development of PET radiopharmaceuticals labeled with generator-produced radionuclides has facilitated greater use of PET in clinical nuclear medicine. The 68Ge/68Ga parent/daughter pair is ideal as a source of PET radiopharmaceuticals as a result of the favorable half-lives of both the parent and daughter radionuclides (43-45). The 271 days half-life of the 68Ge parent... 

The main radiopharmaceuticals labelled with fluorine-18, routinely prepared ([2-i F] fluorodeoxyglucose [ F]FDG [26-28], [i F]fluoro-L-DOPA [29], [i F]altanserin [30, 31], [ F]setoperone [32]) are presented with their uses in Table 2. For comparison, the most common tracers labelled with carbon-11 (methionine [33], palmitic acid [34], flumazenil (RO 15.1788) [35], PK 11195 [36], raclopride [37], deprenyl [38], Way-100635 [39], McN-5652Z [40], CGP 12177 [41]) are shown in Table 3. By far, [ F]FDG is the most widely studied, particularly in oncology for the diagnosis of tumours, detection of sub-clinical diseases, assessment of therapy responses, and detection of recurrence. F-Steroids [42], F-proteins or peptides, or F-labelled tissue specific agents have also been synthesized for the detection and monitoring of various malignancies [43]. 

Design of radiotracers and radiopharmaceuticals labelled with a short-lived positron emitter The case of fluorine-18... 

The main feature of the short-lived positron-emitting isotope F is the relative long half-life of 110 min. The ultrashort-lived isotopes C, N, and O have half-lives of 2-20 min, and they must subsequently be produced in the vicinity of the PET scanner(s). Radiopharmaceuticals labeled with F, on the contrary, can be shipped to distant satellite PET centers that are notequippedwith a cyclotron. Several commercial companies are today producing 2-[ F]fluoro-2-deoxy-D-glucose... 

The NCA radiobromination yields increased from 67.4 2.1% at 135 °C to 92.3 2.2% at 175 °C. The NCA nucleophilic aromatic bromodeiodination is very suitable for syntheses of radiopharmaceuticals labelled with 75Br, 76Br and 77Br. 

Keywords Technetium Rhenium Bioorganometallics Carbonyl Radiopharmaceuticals Labelling... 

LC-MS is a quick and accurate analytical tool for determining the composition of 99mTc radiopharmaceuticals. It also supplements structural information obtained from other analytical methods such as NMR. Therefore, LC-MS may also be a complimentary technique for structure determination of radio-labeled compounds by analyzing the fragmentation patterns of the mass spectra. LC-MS has the potential to become a routine analytical tool for radiopharmaceuticals labeled with 99mTc or other radioisotopes such as 186Re. 

The usual decay process of heavy nuclei is a-particle emission. An a particle is a helium ion containing two protons and two neutrons. Alpha particles are heavy particles that have a very short range in matter due to their mass, and radiopharmaceuticals labeled with a emitters are used only with therapeutic purposes. Their clinical use is very limited, and they are mainly used for research purposes or in early phase clinical studies. 

Although the majority of radiopharmaceuticals labeled with fluorine-18 have been prepared using nucleophilic fluorination reactions, in a few instances the application of electrophilic fluorination reactions has proved quite suitable. The most significant limitation of electrophilic 18F-fluorinations is the relatively low specific activities (less than lOCi/mmol) commonly obtained for final products. This is a result of the fact that electrophilic 18F-fluorination reagents (perchloryl fluoride, acetyl hypofluorite, xenon difluoride, A-fluoro-zV-alkylsulfonamides, diethylaminosulfur trifluoride) are prepared in low specific activity from 18F-labeled fluorine gas, which in itself produced in a carrier-added fashion. A second drawback of electrophilic fluorination is that the maximum radiochemical yield obtainable is 50%, as only one of the two fluorine atoms in fluorine gas can end up in the product (or, for preparation of electrophilic reagents such as acetyl [18F]hypofluorite, the maximum yield of preparing the reagent from [18F]F2 is 50%). 

Table 14.5 Yields of example radiopharmaceuticals labeled with [18F]fluoride ion using nucleophilic substitution reactions performed in protic solvent systems compared with literature methods utilizing aprotic organic solvents...

Boyd RE (1973) Recent developments in generators of " Tc (IAEA-SM-171/94) In Radiopharmaceuticals labelled compounds 1973. IAEA Vienna, pp 3-26 Boyd RE (1982) Technetium-99m generators - the available options. Int J Appl Radiat Isot 33 801-810... 

Radiopharmaceuticals labeled with " Tc are commercially available and are employed in more than 80% of all nuclear medicine investigations. Among the radionuclides, technetium-99m is most attractive to the nuclear medicine physician because of its optimal gamma energy for SPECT, its availability, its relatively low cost, and its easy-to-la-bel kit preparations for in-house use. Another advantage is the low radiation burden to patients, due primarily to its short half-life. The decay within hours also facilitates the handling of waste. 

Many branches of chemistry are involved in nuclear medicine. Nuclear chemistry has developed accelerators and reactors for radionucUde production. Inorganic chemistry has provided the expertise for the development of metal-based radiopharmaceuticals, in particular, Tc radiopharmaceuticals, whereas organic chemistry has provided the knowledge base for the development of PET radiopharmaceuticals labeled with F, "C, and 0. Biochemistry... 

Whilst the work that we focus on in the first part of this chapter concerns the preparation of tritium- and inevitably deuterium-labeled compounds, examples are given where the benefits can also be applied to the carbon ( C, and C)-labeled area [8]. Also discussed is the use of microwaves in the synthesis of radiopharmaceuticals labeled with positron emitters, such as carbon-11 (ti/2 = 20.4 min) and fluorine-18 (ti/2 = 109.7 min). The short half lives of these radioisotopes, together with the requirements for high radiochemical yield (RCY), radiochemical purity (RCP) and specific activity (SA) can benefit from the advantages that micro-waves provide [8, 9]. 

Palmer A.J. Taylor D.M. Radiopharmaceuticals Labeled with Halogen Isotopes. Published as Int. J. Appl.Radiat. Isotopes 37, 645-921, 1986. 

Hot atom chemical techniques are available in production of radiopharmaceuticals labeled with short-lived positron emitters such as and (Iwata and Wolf 1992). These... 

The quality control of radiopharmaceuticals labeled with short-lived radionuclides has to rely on indirect methods for the identification of the compound. Direct methods such as nuclear magnetic resonance (NMR) and infrared spectroscopy cannot be used. Some tests, such as measurement of pH and LC-analysis, can be performed before the radiopharmaceutical is released for use. The radiopharmaceutical is mixed with authentic reference substance and if... 

Basmadjian, G.P., Sadek, S.A., Mikhail, E.A., Parikh, A., Weavei A. and Mills, S.L. (1989) Structure biodistrihution relationship of labeled ergolines Search for brain imaging radiopharmaceuticals. /. Labelled Compd. Radiopharm., 277, 869—883. Benes, J. (1989) Ergolene acetylderivatives and the process for their preparation. CSPat. 

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