Yttrium-90 and Rhenium-188 Radiopharmaceuticals for Radionuclide Therapy

Prior to the animal experiments, the affinity of the radioimmunoconjugates
to CD20 positive Raji cells was measured in vitro. Labelling with 131 I or
111 In and 90 Y by DOTA was performed using standard methods. The various
radioimmunoconjugates were injected intravenously into Burkitt lymphoma
bearing severe combined immunodeficiency (SCID) mice. The biodistribution
was measured at 24, 48, 72 and 96 h p.i. by taking samples of blood, urine,
liver, kidney, spleen, gastrointestinal tract, femur, muscle, thyroid and tumour
and measuring the radioactivity in a well counter. The results were recorded as
percentages of the injected dose per gram organ weight.
5.1.1.3. Results
The dissociation constants obtained for radioimmunoconstruct binding
to tumour cells were in the range 50–90nM. The tumour accumulation for
90 Y DOTA rituximab at 72 h p.i. was significantly higher (2.6-fold) than for
111 In DOTA rituximab ( 90 Y: 69.7%ID/g; 111 In: 25.4%ID/g, 96 h p.i.) (see Fig. 5.1).
Yttrium-90 DOTA rituximab, in contrast to 111 In analogues, showed a markedly
delayed blood clearance, a 2.5-fold higher accumulation in the spleen and
a significantly higher accumulation in bone (threefold). The radiolabelled
radioimmunoconstruct displayed markedly lower accumulation in both tissue and
tumour (tenfold in tumour). The tumour to muscle ratios seemed to be promising,
while tumour to blood ratios were very low. The tumour to background ratios of
90 Y and 111 In DOTA rituximab were not really comparable, but were higher in the
case of the 90 Y labelled antibody (see Fig. 5.2).
5.1.1.4. Conclusion
Indium-111 is not a suitable substitute for 90 Y for measurement of the
accumulation of antibodies in tumours. Yttrium-86 labelled analogues should be
used for reliable pretherapeutic dose calculations for 90 Y radioimmunoconjugates.
Yttrium-90 DOTA rituximab is a promising candidate for radioimmunotherapy.
However, the tumour to background ratios are not good and need to be improved
using pretargeting methods.
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