Radiopharmaceutical preparations

PET imaging systems are somewhat more complex, and therefore more expensive than are SPECT systems, and the price factor is generally between two and three. The primary cost premium associated with these systems, however, is the need for a cyclotron and its attendant staff combined with the relative complexity of radiopharmaceutical preparation for short half-life isotopes. As of 1996, there are considerable hurdles blocking widespread regulatory approval and full reimbursement of PET studies. 

Quality assurance of radiopharmaceutical preparation and use is obviously a very important topic because of its direct impact on patient diagnosis, treatment and health (see, e.g. Abreu 1996). Reference materials play only a small - but nevertheless important -role in this process, mainly in the area of calibration of radioactivity-measuring instruments. The materials of interest are all pure chemical containing calibrated activities of selected radionuclides used commonly in nuclear medicine (e.g. Co, Ga, I,... 

Tc(V) gluconate and glucoheptonate are often used when the reaction should be carried out in a neutral aqueous- or mixed aqueous/organic medium, and a rapid exchange reaction and high radiochemical purity of the product is required. In radiopharmaceutical preparations, Tc(V) tartrate is also quite often used. For labelling modified antibodies Tc(V) tricine has recently been particularly recommended [33],... 

N-Succinimidyl-S-acetylthioacetate) provide efficient ways of introducing multiple sulfhydryl groups for this type of radiopharmaceutical preparation (Chapter 1, Section 4.1). 

Sterility and Pyrogen Testing Sterility indicates the absence of any viable bacteria or microorganisms in a radiopharmaceutical preparation. Hence, sterility testing is performed to prove that radiopharmaceuticals are essentially free of viable microorganism. The test for microbial contamination of these products is best carried out with filter methods. It is a great advantage to incubate only the filters instead of the radioactive solutions. 

A specification for sodium acetate is contained within the Food Ghemicals Godex (FGG). The PhEur 2005 also contains a monograph on sodium acetate [1- G] injection under Radiopharmaceutical Preparations. 

Technetium(III) complexes with aminocarboxylato ligands have been reported but none are well characterized (241). " Tc-iminodiacetate complexes formed with 2,6-alkylphenyl [ArNHCOCH2N(CH2COO)2] " ligands are used to image the hepatobiliary system. Studies with Tc show evidence for [Tc L2]" in the radiopharmaceutical preparations. 

Paragraph 5 contains an exemption for radiopharmaceuticals prepared from an authorised kit, generator or precursor in respect of which there is a marketing authorisation in force, subject to certain conditions. ... 

Sterility. Sterility indicates the absence of any viable bacteria or microorganisms in a radiopharmaceutical preparation. All radiopharmaceuticals must be sterile prior to administration to humans, and it is normally accomplished by filtering the product through a 0.22-pm membrane filter or heating the sample to 120°C for 20 min at a pressure of 18 pounds per square inch. PET radiopharmaceuticals are normally sterilized by filtration because of their short half-life. 

If the reagents in the cold kit are light sensitive, is the radiopharmaceutical prepared from the light-sensitive cold kit also prone to photolytic degradation If... 

Deutsch E, Elder RC, Laarge BA et al (1978) Structural characterization of a bridged technetium-99-tin-dimethylglyoxime complex implication for the technetium-99m-labeled radiopharmaceuticals prepared by tin(II) reduction of pertechnetate. Proc Natl Acad Sci USA 73 653-660 Deutsch E, Glavan KA, Sodd VJ et al (1981) Cationic Tc-99m complexes as potential myocardial imaging agents. J Nucl Med 22 897-907... 

Furthermore, an undesirable side reaction between tin and technetium may occur. As outlined above, there is a high excess of tin - as Sn(II) and Sn(IV) - over technetium and this fact leads to the idea that mixed-metal complexes maybe formed in radiopharmaceutical preparations. Interest in the question, whether stannous or stannic tin could be involved in the radiopharmaceutical was further stimulated by the formation of a tin-capped Tc-dimethylglyoxime complex, Tc(oxime)3(/i-OH)SnCl3 (Deutsch et al. 1976). However, this compound was prepared under the condition of carrier-added technetium its ready conversion to uncapped species gives no evidence for the existence of mixed-metal type compounds. 

The behavior of stannous ion in kit preparations has been studied in a limited number of compounds, and the conclusion reached so far indicates that, apparently, tin ions only reduce TcOj and indeed, apart from some tin-essential preparations such as stannous oxide colloid labeled with " Tc (Subramanian and McAfee 1970), mixed Tc-Sn complexes have not been observed in low-molecular-weight radiopharmaceutical preparations. 

S, Klenscdr Z (eds) Radiochemistry and radiopharmaceutical chemistry in life science, handbook of nuclear chemistry, vol. 4. Kluwer, Dordrecht, pp 211-256 Alvarez J (1975) Radiopharmaceuticals prepared with stannous chloride. J Radioanal Chem 27 475-482... 

Technetium-99m ( Tc) is widely used in radiopharmaceutical preparations due to its excellent physical and chemical properties. In fact, more than 80% of all radiopharmaceuticals used in diagnostic nuclear medicine are based on this short-lived radionuclide, which is obtained by elution of a Mo/ Tc generator system that is available in any radiopharmacy and nuclear medicine facility. 

Radiopharmaceutical preparations (01/2005 0125). This monograph describes the principles and methods to be applied in the respective paragraphs of the individual monographs, e.g., how to measure the half-life of a radionuclide. 

Radiopharmaceuticals prepared in a nuclear medicine department using licensed labeling kits (mostly Tc-labeled preparations) need not to be analyzed after their preparation according to the Ph. Eur. monograph, but rather, follow the instructions in the package leaflet. In most cases, this means a rather simple check of the radiochemical purity and in some cases, of the pH. However, if for any reason a full analysis is required (e.g., in case of serious side effects), these preparations must meet all requirements of the monograph. 

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