11 DESCRIPTION The active ingredient in Lymphoseek is technetium Tc 99m tilmanocept. The active ingredient is formed when Technetium Tc 99m pertechnetate, sodium injection is added to the Tilmanocept Powder vial.

Technetium Tc 99m binds to the diethylenetriaminepentaacetic acid (DTPA) moieties of the tilmanocept molecule.

Chemically, technetium Tc 99m tilmanocept consists of technetiumTc 99m, dextran 3-[(2-aminoethyl)thio]propyl 17-carboxy-10,13,16- tris(carboxymethyl)-8-oxo-4-thia-7,10,13,16-tetraazaheptadec-1-yl 3-[[2-[[1-imino-2-(D- mannopyranosylthio) ethyl]amino]ethyl]thio]propyl ether complexes. The molecular formula of technetium Tc 99m tilmanocept is [C6 H10 O5 ]n .(C19 H28 N4 O9 S99m Tc)b .(C13 H24 N2 O5 S2 )c .(C5 H11 NS)a . It contains 3-8 conjugated DTPA (diethylenetriamine pentaacetic acid) molecules (b); 12-20 conjugated mannose molecules (c) with 0-17 amine side chains (a) remaining free. The calculated average molecular weight of tilmanocept ranges from 15,281 to 23,454 g/mol. Technetium Tc 99m tilmanocept has the following structural formula:

 
(click image for full-size original) Lymphoseek (technetium Tc 99m tilmanocept) Injection is supplied as a Kit. The Kit includes Tilmanocept Powder vials which contain the necessary non-radioactive ingredients needed to produce technetium Tc 99m tilmanocept. The Kit also contains DILUENT for Lymphoseek. The diluent contains a preservative and is specifically formulated for Lymphoseek. No other diluent should be used.

The Tilmanocept Powder vial contains a sterile, non-pyrogenic, white to off-white powder that consists of a mixture of 250 mcg tilmanocept, 20 mg trehalose dihydrate, 0.5 mg glycine, 0.5 mg sodium ascorbate, and 0.075 mg stannous chloride dihydrate. The contents of the vial are lyophilized and are under nitrogen.

The DILUENT for Lymphoseek contains 4.5 mL sterile buffered saline consisting of 0.04% (w/v) potassium phosphate, 0.11% (w/v) sodium phosphate (heptahydrate), 0.5% (w/v) sodium chloride, and 0.4% (w/v) phenol. The pH is 6.8 – 7.2.

11.1 Physical Characteristics Technetium Tc 99m decays by isomeric transition with a physical half-life of 6.02 hours. The principal photon that is useful for detection and imaging studies is listed in Table 6.
Table 6: Principal Radiation Emission Data From: Kocher, D.C. Radioactive decay data tables. DOE/TIC-11026, 108 (1981).
Radiation Mean % Disintegration Mean Energy (keV)
Gamma-2 89.07 140.5
11.2 External Radiation The linear mass energy absorption attenuation coefficient for Tc 99m is 18.986 cm-1. The first half-value layer is 0.037 cm of lead (Pb). The use of a 0.25 cm thick standard radiation lead shield will attenuate the radiation emitted by millicurie amounts of technetium Tc 99m by a factor of about 100. A range of values for the relative attenuation of the radiation of technetium Tc 99m that results with various thicknesses of lead shielding are displayed in Table 7.

Table 7: Radiation Attenuation by Lead Shielding Shield Thickness, cm of lead (Pb) Coefficient of Attenuation
0.037 0.5
0.12 10-1 
0.24 10-2 
0.36 10-3 
0.49 10-4 
To correct for physical decay of the radionuclide, the fractions that remain at selected intervals after the time of calibration are shown in Table 8.

Tabl