Yttrium-90 and Rhenium-188 Radiopharmaceuticals for Radionuclide Therapy

to avidin at the 1:4 avidin:r-BHD molar ratio. A blank HABA assay using only
89 YCl 3 showed no influence in the displacement of HABA from the binding sites
of avidin. The new 90 Y r-BHD compound was tested in a pilot study according
to the pretargeting IART protocol. The trial showed a lack of haematological,
major kidney and local toxicity of the treatment, and provided partial irradiation
therapy immediately after surgery, thus allowing reduction of the duration of a
standard course of whole breast external beam radiation therapy.
Although these encouraging data may justify randomized trials in a large
patient population, the microbiological safety of the locally labelled 90 Y r-BHD
may hamper its wider use. Therefore, the labelling conditions in an automatic
module of synthesis (PharmTracer) fitted with a disposable sterile single use
kit were tested [7.20]. The remotely controlled steps of purification through a
C18 cartridge to eliminate the unbound 90 Y and the final filtration through a
sterilizing 0.22 μm filter allowed a safe injectable product to be obtained. In
addition, the module is capable of performing, at the end of the synthesis, a
test to check the filter integrity by applying gas pressure and comparing with
a closed system, as recommended by good manufacturing practice rules to
ensure the sterility of the final product. A secondary objective related to the use
of the automated module was to evaluate whether its use decreased the finger
radiation dose of the operator [7.21]. Preliminary measurements showed that
finger radiation exposure decreased twofold using this automatic remote system
compared to the previously used manual procedure, namely from 12 µSv/GBq to
5.4 µSv/GBq (see Fig. 7.4).
7.5. CONCLUSION
In the time frame of this CRP, a new biotin DOTA derivative was
developed, and labelling conditions with the therapeutic radionuclide 90 Y
were optimized. Implementation of an automatic module for the synthesis of
the radiopharmaceutical 90 Y DOTA biotin with a high RCP and sterility may
represent a step forward in the spread of the IART approach in clinical trials.
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