Orner Jeghers

What does protein binding of radiopharmaceuticals mean exactly

The in vivo reversible and non-reversible interactions of small molecules with macromolecules such as proteins are of great importance in biology due to their interference with biodistribution, the rate of elimination and access to the action site, and with metabolism. In nuclear medicine, it is essential that we understand and quantify this phenomenon in order to anticipate the behaviour in vivo of radiotracers. Indeed, some tracers such as technetium 99m dimercaptosuccinic acid (DMSA) or 99mTc-iminodiacetic acid (IDA) have to be bound to the blood proteins. 99mTc-DMSA is then taken up by the renal protein receptors containing sulfhydryl groups (Moretti e ta l . 1984), whereas 99mTc-IDA is transferred by albumin from the sinusoid to the hepatic cell (Firnau 1976). On the other hand, the substances that measure the glomerular filtration rate should not bind to protein (Rao Chervu et al. 1974). Therefore, the evaluation of a new radiomolecule necessarily includes the measurement of protein binding. However, the data reported in the literature are often disconcerting. For example, several authors have recent-

A chemical method for the labeling of fibrinogen with 99mTc

A new method allowing the labelling of fibrinogen with 99mTcO4-is described. The 99mTcO4-is reduced by stannous chloride in an alkaline medium. After 1 h incubation with fibrinogen, the pH was brought down to 7.1. The study of (1) the pH of the solution, (2) the quantity of the reducer, and (3) the time of incubation allowed us to specify optimal conditions for labeling. The labeling yield varied from 91.68%±6.05% to 95.18%±2.13% according to the method of control used: the precipitation of fibrinogen by (NH4)2SO4 25% or thin-layer chromatography with methylethylketone as solvent. Clottable radioactivity averaged 72%±4.43%. Column chromatography separated the tracer into two radioactive peaks. The first peak corresponded to the fibrinogen and carried 73.36%±5.8% of the total radioactivity. The total recovered radioactivity amounted to 89.86%±8.07%. Spectroscopic clottability was 88.23%±2.42%.The in vivo stability of the labeling and the molecule was followed for 24 h after intravenous injection. If the radioactivity measured in the 5 min sample was considered to equal 100%, the 24 h sample averaged 32.71%±3.25%, of which 85.68%±2.92% was recovered in the clot. In conclusion, this method enabled us to obtain a stable tracer that we used for routine investigations in man.

The interpretation of phlebograms using fibrinogen labeled with 99mTc

A new method for the detection of deep-vein thrombosis is presented, consisting of a single antecubital injection of fibrinogen labeled with 99mTc. This atraumatic procedure allows one to visualize the large veins of the lower limbs, the venae iliacae and the distal part of the vena cava inferior. This paper discusses how to interpret these phlebograms.

Comparison of two 99mTc(V)-dimercaptosuccinic acid preparations.

99mTc(V)-DMSA labelled either by increasing the pH together with a low concentration of Sn, or by increasing the pH only are compared in vitro and in vivo. The gel chromatographic separation shows that after incubation with blood, all the 99mTc(V)-DMSA preparations are stable and do not bind to the plasma proteins. The behavior in rats as well as in clinical studies does not demonstrate any distinctive characteristics between the different radiomolecules. It seems that the pH of the solution is an important factor which controls the formation of 99mTc(V)-DMSA.

Aminopyrine breath test in alcoholic cirrhosis

SummaryAminopyrine breath test was performed in 91 consecutive alcoholic cirrhotic patients in order to evaluate its clinical value in this group of patients. As compared with routine liver biochemical tests, aminopyrine breath test was found to be altered most frequently (93.5% of cases). A one-year follow-up was obtained in 69 patients. The one-year mortality rate was only 11% for values of aminopyrine breath test ≥ 2%, whereas it reached 53.5 for results inferior to 2%. The prognostic value of the test was not, however, different from that of the Child-Turcotte classification.

Per rectal thallium scintigraphy for the assessment of portosystemic shunt: an experimental study in the bile duct ligated rats

Bile duct ligated rats (n=7) have been investigated for 6 months. Two patterns of evolution have been observed: (i) progressive development of cirrhosis and portosystemic shunt (detected by 201Tl per rectal scintigraphy) in three animals, (ii) repermeabilization of the biliary tract in four animals. Despite the small number of animals investigated, the 201Tl per rectal scintigraphy seems to be a good indicator of portosystemic shunt secondary to biliary cirrhosis.