Radiopharmaceuticals specific activities

For the synthesis of high-specific-activity radiopharmaceuticals (specific activity is defined as radioactivity per unit mass) the use of [18F]fluoride ion is preferred if not required. The theoretical specific activity for fluorine-18 is 1.71 x 109Ci/mol, but that value has never been achieved and in practice the specific activity of 18F-labeled radiochemicals has been significantly lower. Typically, finished radiochemicals are produced with specific activities in the 1000-10 000 Ci/mmol. Some of this difference has been attributed to physical dilution of the fluorine-18 by the presence of fluorine-19 in... 

An important consideration for all radiopharmaceuticals and especially radiolabeled biologically active molecules is specific activity. There are two types of specific activity radionucHdic and biological. RadionucHdic specific activity refers to the ratio of the number of atoms of a particular radioisotope to the total number of atoms of the element. For Tc, the radionuchdic specific activity is the number of Tc atoms to the total number of Tc and Tc atoms. Because all isotopes of an element ate chemically identical, a low specific activity may lead to a low yield in the synthesis of a radiopharmaceutical if a significant proportion of the reagents is consumed by the undesited isotopes. 

Chelating Moieties for Preparation of High Specific Activity 99m Xc-Radiopharmaceuticals... 

Specific activity of a radiopharmaceutical may be defined as the amount of radioactivity per unit mass of a radioisotope or a labeled compound. For example, if 100 mg l3lI-labeled albumin contains 150 mCi l3lI radioactivity, its specific activity would be 150/100, i.e., 1.5 mCi/mg. Specific activity is usually expressed in units such as Ci/g, mCi/mg, or MBq/mg. It is also expressed in terms of the radioactivity per mole of a labeled compound, e.g., mCi/mole, MBq/mole, mCi/pmole, or MBq/p,mole. Specific activity is usually provided on the product label. 

A series of fluorine-18 labelled 1,2-diazabenzenes 6 have been synthesized28 in the reaction of high specific activity, NCA [18F]fluoride ion with various chloro-substituted pyridazines 7 (equation 8) in radiochemical yields ranging from 11 to 64% [24% yield for R = Me, 64% for R = 4-benzoyl, 11% for R = 4-fluorobenzoyl, 46% for R = (2-thienyl) carbonyl]. The rat biodistribution of pyridazine analogues, more polar than the corresponding phenyl derivatives, has been studied and their applications to radiopharmaceuticals are underway28. 

Radiopharmaceuticals used for receptor studies have to be labelled with high specific activity in order to avoid saturation of the receptor sites. Various [18F]fluoroaromatic aldehydes and benzyl bromides have been synthesized41 according to equation 18 in 50-75% (EOB) radiochemical yields and 30-50% EOB radiochemical yields, respectively. 

Indolealkylamines, [ Cj-dimethyltryptamine (UC-DMT, 304), [nC]-5-methoxy-A,iV-dimethyltryptamine ([uC]-5-OMe DMT, 305) and [nC]-bufetenine 306, known to have hallucigenic properties285 and expected to serve as potential serotonin-1 receptor mapping radiopharmaceuticals, have been synthesized286 (equation 119) in 46%, 18% and 8.9% overall radiochemical yields, respectively, with average specific activity of 63 Ci mmol"1 at the time of use. 

General Considerations The synthesis of PET radiopharmaceuticals has several peculiarities substantially different from the procedures followed to prepare conventional y-emitting radiopharmaceuticals. A very important issue that must be considered is the specific activity. For all radiopharmaceuticals it is usually very high and can be calculated from the formula... 

As discussed already, radiopharmaceuticals are exposed to stability problems, particularly when radiolabeled compounds are involved. Decomposition of labeled compounds by radiolysis depends on the specific activity of the radioactive material, the energy of the emitted radiation, and the half-life of the radionuclide. Particles, such as a and p radiation, are more damaging than y rays, due to their short range and local absorption in matter. The stability of a compound is time dependent on exposure to light, change in temperature, and radiolysis. The longer a compound is exposed to these conditions, the more it will tend to break down. 

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%). 

Despite the low specific activity obtained with electrophilic 18F-fluorination reagents, important radiopharmaceuticals have been prepared in this fashion. 

The physical and chemical properties of Lu make it an excellent radio-nuchde for the development of therapeutic radiopharmaceuticals. The specific activity and chemical purity of Lu are critical factors that influence stabihty, labelling yield and receptor mediated uptake. The field of therapeutic radiopharmaceuticals will benefit greatly from the availability of high specific activity Lu at a reasonable cost. Some of the participants have begun producing Lu using the research reactors available in their countries. 

---