Low-specific activity

Eor products having relatively low specific activity, such as some compounds labeled with and which are synthesized on the scale of several millimoles, classical organic chemical separation methods may be utilized, including extraction, precipitation, and crystallization. Eor separation of complex mixtures and for products having high specific activity, such as those labeled with tritium, etc, chromatographic methods utilizing paper, thin... 

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. 

AH cephalosporins found in nature (Tables 1 and 2) have the D-a-aminoadipic acid 7-acyl side chain (21). AH of these compounds can be classified as having rather low specific activity. A substantial amount of the early work in the cephalosporin area was unsuccessfiiHy directed toward replacing the aminoadipic acid side chain or modifying it appropriately by fermentation or enzymatic processes (6,22). A milestone ia the development of cephalosporins occurred in 1960 with the discovery of a practical chemical process to remove the side chain to afford 7-ACA (1) (1). Several related processes were subsequendy developed (22,23). The ready avaHabHity of 7-ACA opened the way to thousands of new semisynthetic cephalosporins. The cephalosporin stmcture offers more opportunities for chemical modification than does that of penicillins There are two side chains that especiaHy lend themselves to chemical manipulation the 7-acylamino and 3-acetoxymethyl substituents. 

The dose of TCDD given to the male rats used in this study, 50 />tg/kg, was approximately twice the LD50, 23 /xg/kg. This large dose was necessary because of the low specific activity of the TCDD- C used. In this study rats lost weight, and their physical condition was poor, which typifies the insidious response to TCDD (J). Survival of the rats for 21 days was not totally unexpected because in previous studies on the lethality of TCDD deaths frequently occurred 20 or more days following a single oral dose of similar magnitude (I). With doses that do not induce untoward effects, the compound may be excreted at a different rate. 

Although quite extensive use of has been made in studies on the degradation of alkyl sulfonates (Hales et al. 1986), C1 has achieved only limited application on account of technical difficulties resulting from the low specific activities and the synthetic inaccessibility of appropriately labeled substrates. One of the few examples of its application to the degradation of xenobiotics is provided by a study of the anaerobic dechlorination of hexachlorocyclohexane isomers (Jagnow et al. 1977), the results of which are discussed in Chapter 7, Part 3. 

Reactors are sources of neutrons, and thus most reactor-produced radionuclides are neutron-rich ft emitters. Reactor-produced radionuclides are of relatively low specific activity if the target nucleus is the same element as the product radionuclide, because the target and the product cannot then be chemically separated. 

This yields 89Sr in low specific activity however, this is sufficient for use as a pain palliation agent in metastatic bone disease. 

The 153Sm produced has low specific activity because it is heavily outnumbered by and cannot be chemically separated from the 152Sm target. 

When lanthanides are injected, even in citrate solutions, with added stable carrier or as low-specific-activity reactor-produced tracers (a) most of the activity, even of those lanthanides that usually deposit in bone, is shunted to liver and spleen (b) in rodents the loss of the liver burden is delayed (c) the deposition in spleen is high and (d) autoradiographs demonstrate reticuloendothelial uptake in liver and spleen (Durbin et al., 1956a Moskalev, 1961b Thomas et al., 1971). 

Figure 2. Electrophoretic profiles of glucan synthase fractions purified from celery. Proteins were transferred to nitrocellulose and stained by colloidal gold. Symbols PM, plasma membranes SOL, CHAPS-solubilized RC, reconstituted glucan synthase preparations. Plasma membranes were isolated by two-phase partitioning. Specific activities of the three membrane preparations were 398, 1355, and 626 nmol/min/mg, respectively. The low specific activity of RC relative to SOL may be a reflection of enzyme instability following the gel filtration step.

Sulphur fefra[ F]fluoride (S[ F]F4) was obtained by irradiation of a neon-SF4 mixture, giving rise to a low-specific-activity product by fluorine-18 for fluorine exchange. It was used as an alternative to H[ F]F in the preparation of [ F] DAST [57], S[ F]F4 has not found other applications so far. 

One may conclude that the above-mentioned anhydrous [ F]fluorine compounds, except perhaps H[ F]F, have been abandoned, partly because of their limited potential and difficulty of preparation and also because of the success of the main three agents of today, [ F]fluoride (see Section 4), p F]fluorine gas (see Section 3.1.1) and acetyl [ F]hypofluorite (see Section 3.1.3). The advent of the first one, ([ F]fluoride), made less urgent the need for high-specific-activity electrophilic fluorine and the latter two, ([ F]fluorine gas and acetyl p F]hypo-fluorite), are able to perform practically all low-specific-activity electrophilic syntheses (see Section 3), putting a brake on the development of alternatives. 

Inhibitors known to be selective for MAO A or B have been labeled with P F]-fluorine for PET studies. For example, [ F]-fluoroclorgyline (35) labeled on the aromatic ring with low specific activity [ F]-fluorine was shown to have favorable properties for mapping MAO A activity in the brain [103],... 

An industrial process to produce methanol from carbon monoxide and hydrogen was developed by BASF in 1923 using a zinc oxide-chromia catalyst.361 362 Since this catalyst exhibited relatively low specific activity, high temperature was required. The low equilibrium methanol concentration at this high temperature was compensated by using high pressures. This so-called high-pressure process was operated typically at 200 atm and 350°C. The development of the process and early results on methanol synthesis were reviewed by Natta 363... 

If only melting occurs, an explanation for the bell-shaped distribution of specific activity must take into account an incursion of material of low specific activity at the small sizes which still experienced sufficiently high temperatures to melt. 

The kinetic parameters Km, V, ax, pH optima, and energy of activation (2 act) for deamination of adenosine catalyzed by homogeneous preparations of adenosine aminohydrolase are summarized in Table III 82-86, 98). Except for the unusually low specific activities observed for both the chicken duodenal and calf serum enzymes, and the significantly higher energy of activation reported for the former, the reaction param-... 

The effect of specific activity on the cost of the remote second encapsulation is shown in Figure 6. Costs depend somewhat on batch size but are reduced dramatically by an increase in specific activity. The reasons for this are obvious from the example we chose. At 200 curies per gram we are remotely encapsulating only 40 strips at 20 curies per gram, 400 and at 2 curies per gram, 4000. The second encapsulation costs for our 670,000-curie example would be approximately 13,500, 27,000, and 142,000 for the high to low specific activities, respectively. 

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