Yttrium-90 and Rhenium-188 Radiopharmaceuticals for Radionuclide Therapy

13.2.3. Dithiocarbamate bisphosphonate conjugates
A new bifunctional ligand 7, comprising a bisphosphonate group
conjugated to a dithiocarbamate, was synthesized with a view to preparing
bis(bisphosphonate) complexes using the pentavalent rhenium and technetium
nitride cores (see Fig. 13.15). The methodology for the ligand synthesis has
been described previously [13.30–13.32]. The solution of 6 used in these studies
contained 10 times more non-labelled bisphosphonate than there was in the
99m Tc MDP solution. To test the inhibition properties of 3, the same binding
studies were carried out with HA and CO in the presence of an excess of 3,
resulting in the complete inhibition of binding of 6.
Radiolabelling to produce the 99m Tc complex 9 was achieved by first making
a Tc ≡ N 2+ intermediate [13.22, 13.23] as follows. Succinic dihydrazide (2.5 mg)
and 1,2-diaminopropane-N,N,N’,N’-tetraacetic acid DPTA (1 mg) were dissolved
in 0.5 mL saline. Technetium-99m pertechnetate generator eluate (700 MBq,
0.12 mL) was then added, followed by 30 μL of a 10 mg/mL solution of SnCl 2 in
0.05M HCl. The mixture was then incubated with shaking at room temperature for
30 min. After this time, TLC was performed using aluminium backed SG plates in
a solvent system of 6:3:3:1 ethanol:chloroform:toluene:0.5M ammonium acetate,
in which pertechnetate had R f = 0.5 and was shown to be absent. A volume of
300 μL of the 99m TcN 2+ intermediate thus prepared was added to 200 μL of
50mM sodium carbonate buffer containing 0.5 mg of the DTC bisphosphonate
ligand 7, followed by shaking at 60°C for 25 min to give 9. TLC was performed
(silica on alumina TLC) using MeOH and 1% of 60% HEDP solution. Here,
97% of the activity was retained at the origin, showing that only 3% of the activity
FIG. 13.15. Synthesis of dithiocarbamate bisphosphonate ligand 7 and its 99m Tc complex 9.
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