TECHNETIUM (99mTc) MACROSALB INJECTION Definition Technetium (99mTc) macrosalb injection is a sterile, a pyrogenic suspension of human albumin in the form of irregular insoluble aggregates obtained by denaturing human albumin in aqueous solution The injection contains reducing substances, such as tin salts in an amount not exceeding 3 mg of Sn per millilitre; it may contain a suitable buffer such as acetate, citrate or phosphate buffer and also non-denatured human albumin and an antimicrobial preservative such as benzyl alcohol. The human albumin employed complies with the requirements prescribed in the monograph on Human albumin solution (0255).

The injection contains not less than 90.0 per cent and not more than per cent of the declared technetium-99m radioactivity at the date and hour stated on the label. The specific radioactivity is not less than 37 MBq of technetium- 99m per milligram of aggregated albumin at the date and hour of administration. It is prepared from sodium per technetate (99mTc) injection (fission or non-fission) using suitable sterile and a pyrogenic ingredients and calculating the ratio of radionuclidic impurities with reference to the date and hour of administration. Properties of technicium A white suspension which may separate on standing. Technetium-99m has a half-life of 6.02 h and emits gamma radiation.

Measurement of radioactivity Non-filterable radioactivity Use a polycarbonate membrane filter 13 mm to 25 mm in diameter, 10 μm thick and with circular pores 3 μm in diameter. Fit the membrane into a suitable holder. Place 0.2 ml of the injection on the membrane and filter, adding 20 ml of a 9 g/l solution of sodium chloride R during the filtration. The radioactivity remaining on the membrane represents not less than 90 per cent of the total radioactivity of the injection. Particle size Place a suitable volume in a suitable counting chamber such as a haemocytometer cell, taking care not to overfill the chamber.

Scan an area corresponding to at least 5000 particles. Not more than 10 particles have a maximum dimension greater than 100 μm. No particle having a maximum dimension greater than 150 μm is present. Aggregated albumin Test solution. Transfer a volume of the injection expected to contain about 1 mg of aggregated albumin to a centrifuge tube and centrifuge at about 2500 g for 5 min to 10 min. Decant the supernatant liquid. Resuspend the sediment in 2.0 ml of a 9 g/l solution of sodium chloride R. Centrifuge at 2500 g for 5 min to 10 min. Decant the supernatant liquid.

Resuspend the sediment in 5.0 ml of sodium carbonate solution R1. Heat in a water-bath at 80 °C to 90 °C to dissolve the aggregated albumin. Allow to cool, transfer to a volumetric flask and dilute to 10.0 ml with sodium carbonate solution R1. Reference solutions A range of reference solutions containing 0.05 mg to 0.2 mg of human albumin per milli litre in sodium carbonate solution R1. Introduce 3.0 ml of each solution separately into 25 ml flasks. To each flask add 15.0 ml of cupri-tartaric solution R2, mix and allow to stand for 10 min. Add rapidly 1.5 ml of dilute phosphomolybdotungstic reagent R and mix immediately. Allow to stand for 30 min and measure the absorbance (2.2.25) at 750 nm using sodium carbonate solution R1 as the compensation liquid. Using the absorbances obtained with the reference solutions, draw a calibration curve and calculate the content of aggregated albumin in the injection.

Assay Inject a volume not greater than 0.2 ml into the caudal vein of each of three rats weighing 150 g to 250 g. Kill the rats 15 min after the injection, remove the liver, the spleen and the lungs and measure the radioactivity in the organs using a suitable instrument. Measure the radioactivity in the rest of the body, including the blood, after having removed the tail. Determine the percentage of radioactivity in the lungs, the liver and the spleen from the expression : Percentage of radioactivity = A/B X 100 A = radioactivity of the organ concerned, B = total radioactivity in the liver, the spleen, the lungs and the rest of the body.

Note : In not fewer than two of the three rats used, at least 80 percent of the radioactivity is found in the lungs and not more than a total of 5 per cent in the liver and spleen. The injection may be released for use before completion of the test. Radioactivity Measure the radioactivity using suitable counting equipment by comparison with a standardised technetium-99m solution or by measurement in an instrument calibrated with the aid of such a solution. Pyrogens It complies with the test for pyrogens prescribed in the monograph on Radiopharmaceutical preparations (0125). Inject into the animals not less than 0.1 ml per kilogram of the rabbit’s mass. The injection may be released for use before completion of the test.

The label states : The preparation should be shaken before use, The quantity of tin per millilitre, if any, The preparation is not to be used if after shaking, the suspension does not appear homogeneous. Applications Bone scan Myocardial perfusion imaging Cardiac ventriculography Functional brain imaging Sentinel-node identification Immunoscintigraphy