Radiopharmaceuticals isotope production

T.J. Ruth, Accelerators available for isotope production, in M.J. Welch, C.S. Redvaniy (Eds.), Handbook of Radiopharmaceuticals—Radiochemistry and Applications, Wiley, Chichester, 2003, pp. 71-86. 

Ruth TJ (1985) Int J Appl Radiat Isot 36 107 Ruth TJ (2003) Accelerators available for isotope production. In Welch MJ, Redvanly CS (eds) Handbook of radiopharmaceuticals. Wiley, Chichester, pp 71-83 Ruth TJ, Wolf AP (1979) Radiochim Acta 26 21 Scholten B, Kovacs Z, Tarkanyi F, Qaim SM (1995) Appl Radiat Isot 46 255... 

The CP-42 was finally finished and running in 1983, with isotope production slated for the following year. (The first cyclotron-produced isotopes had been shipped from the large cyclotron in 1982.) Most of the CP-42 products were delivered as bulk isotopes to radiopharmaceutical companies, which would then refine them into final products ready for use in humans. Many of these... 

A particularly useful application of MW-assisted synthesis at elevated pressure has been in the preparation of radiopharmaceuticals containing isotopes with short half-lives, such as C-ll (half-life 20 min) and F-18 (half-life 110 min) [25-27]. Clearly, these compounds have to be synthesized very rapidly in order to give products with high radiochemical yield. For example, [1-11C] tyrosine 12 was synthesized using the two step Bucher-Strecker method by the reaction of p-hydroxyphenylacetaldehyde bisulfite adduct 11 with K11CN and (NH4)2C03 followed by hydrolysis with aqueous NaOH (Scheme 4.7)... 

Radiopharmaceuticals. Radioactive isotopes for human use in the diagnosis and treatment of disease states are called radiopharmaceuticals. Whereas the dosage form types used, e.g., solutions or injections, are traditional, special handling of these products during compounding, transport, and use is vital. Most are administered intravenously and shortly after preparation. Specialized pharmacies prepare these products overnight and transport them to hospitals for early administration by members of nuclear medicine departments. 

A radiopharmaceutical is any medicinal product which, when ready for use, contains one or more radionuclides (radioactive isotopes) included for a medicinal purpose. This generic definition of radiopharmaceutical thus includes both diagnostic and therapeutic radiopharmaceuticals. 

Positron emitting nuclides have very short half lives, on the order of minutes to tw o hours. This makes operation of a cyclotron and a radiochemistry laboratory essential to the use of PET scanners. is the longest radionuclide with a half-life of 1.87h, making a central production facility within a city feasible for radiopharmaceuticals employing this nuclide. Most clinical PET facilities have on-site cyclotrons and radiopharmaceutical laboratories to allow the use of short-lived isotopes in clinical studies. 

The CRP work plan was proposed at the project s first Research Coordination Meeting (RCM), held in Bucharest in October 2002. The evaluation of a new therapeutic radiopharmaceutical depends on several analytical techniques to establish the product s stability and chemical, radiochemical and pharmaceutical purity. In addition, specific bioassays must be developed to evaluate its biological efficacy. These bioassays are product specific and thus need to be worked out separately for each radiopharmaceutical. Participants also identified potential lead molecules and isotopes to be used during the CRP for the development of therapeutic radiopharmaceuticals. 

Dedicated equipment shall be available for production of chemical drugs such as hormones and anti-cancer drugs there shall be dust prevention and extraction facilities and the air exhausted shall be filtered before discharge. Areas for radiopharmaceuticals production shall comply with the requirements for radio-protection and be used by a holder of the certificate of using isotopes. 

Radiopharmacy is a discipline concerned with the preparation and quality control of radiopharmaceuticals. The term radiopharmacy is also used for the pharmacy where these activities are carried out Radiopharmaceuticals are medicinal products that contain radionuclides (radioactive isotopes). Radionuclides are produced in nuclear reactors or in cyclotrons. The most important radionuclides used in nuclear medicine are technetium and fluoride. 

CPD took the diversification initiated with TRIUMF a step further in 1978, when it decided to move into production of radiopharmaceuticals (known as labelled or ta ed isotopes in the early days of CPD). For years CPD had supphed bulk isotopes to pharmaceutical companies. Now it decided that processing radioisotopes into compounds ready for medical use oflFered an opportunity for growth and profit that it could no longer ignore. The production of radiopharmaceuticals required more precision and stricter quality controls than the manufacture ofbulk isotopes, so in 1980 the isotopes branch created a special group to develop these products. 

In its nuclear medicine business, MDS Nordion remains the world s number one producer of medical isotopes. Radiopharmaceutical producers on five continents use its radioisotopes to make their products. It supplies two-thirds of the reactor-produced isotopes used in the world as well as a wide variety of cyclotron-produced isotopes. Its market leadership continues to be based in its position as the leading supplier of molybdenum-99, the source of technetium 99m, the most important isotope for nuclear medicine. While planning to strengthen its position as the leading supplier of bulk isotopes, MDS Nordion continues to look to the development of its own radiopharmaceutical products as the key to growth in the future. Many of these products help detect medical conditions, but some of the latest ones can aaually treat diseases. MDS Nordion is already selling radiopharmaceuticals for certain types of cancer therapy. 

Owing to the short half-lives of the radioactive isotopes involved (e.g., t n of carbon-ll=20min, ty-i of fluorine-18 = 110min), radiopharmaceuticals for PET (and related SPECT) imaging are typically produced on-site daily or at facilities in close proximity to the PET imaging center. Radiopharmaceutical production typically requires trained radiochemists, with specific and expensive facilities. Moreover, the short-lived radionuclides involved means that radiochemical reactions must be fast, efficient, and amenable to automation, and new techniques that facilitate radiopharmaceutical production and the ability to meet clinical demand for PET tracers are in demand. Solid-phase synthesis is an attractive synthetic technique to the radiochemist as it bears many of these desirable characteristics. Despite this, solid-phase organic radiosynthesis (SPOR) is a relatively new... 

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