Yttrium-90 and Rhenium-188 Radiopharmaceuticals for Radionuclide Therapy

was in the form of either pertechnetate or 99m TcN 2+ . For biological evaluation,
80 μL of 0.1N HCl was added to 200 μL of the product solution to adjust the pH
to between 6.7 and 7.0, giving a final activity 101 MBq in 280 μL.
The affinity of 9 for calcium based minerals including HA was
assessed by incubating the tracer with 1 mg/mL solutions of the salts in tris
buffer (50mM, pH6.9), followed by centrifugation, using the 99m Tc nitride
intermediate 8 as a negative control, which showed negligible binding to all
minerals. The 99m TcN DTC bisphosphonate complex 9 showed high percentage
incorporation into all minerals, especially HA (~90%) (see Fig. 13.16). The
binding to HA was also measured using human serum as the incubation medium
and compared with 99m Tc MDP. Complex 9 retained much higher affinity for HA
in the serum than did 99m Tc MDP (see Fig. 13.17).
The affinity for HA in serum over a prolonged period (24 h) suggests that
9 should be evaluated in vivo as a bone targeting tracer. Accordingly, mice were
given tail vein injections of 40 MBq 9 (volume = 0.1 mL) and scanned using a
nanoSPECT scanner for up to 6 h. The affinity for bone and low soft tissue uptake
was evident (see Fig. 13.18), while both bone uptake and renal clearance were
slower than for the commercial radiopharmaceutical 99m Tc MDP (see Fig. 13.19),
which was studied in parallel as a standard reference bone imaging agent.
Although uptake in bone was slower, the absolute percentage of injected dose per
gram eventually reached significantly higher levels than for 99m Tc MDP.
FIG. 13.16. Binding of 99m Tc bisphosphonate conjugate 9 to calcium salts.
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