Yttrium-90 and Rhenium-188 Radiopharmaceuticals for Radionuclide Therapy

fact that radioimmunoconstructs with complete antibodies display higher tumour
uptake than those based on antibody fragments. The complete antibody has a
longer half-life in the blood than antibody fragments, which gives the antibody a
longer period of contact with the surface antigens on the tumour cells [2.51].
2.3.3.3. Pretargeted radioimmunotherapy
Tumour selectivity can be increased by means of bispecific antibodies;
this is the principle behind multistage radioimmunotherapy in the form of
so-called pretargeting. Here, the tumour tissue is first presented with a bispecific
antibody. After the antibody has accumulated sufficiently on the tumour and
after forced clearance of the antibody from the blood pool by a clearing agent,
radioactively labelled therapeutic component with a higher affinity for the
respective binding site of the bispecific antibody is applied. In the last step of this
multistage process, radioactivity is finally brought selectively to the tumour cells
while normal tissue is left unscathed. The ideal situation is to create an avidin,
streptavidin or biotin binding site within the structure of the antibody. Biotin
avidin binding constitutes one of the most stable bonds known. The respective
binding partner can then be applied with a labelled therapeutic radionuclide.
Promising preliminary results from clinical trials have already been reported.
However, this radioimmunotherapeutic approach still needs fine tuning with
regard to the setting of intervals between applications and optimal dosage of the
active substances [2.52].
2.3.4. Radioreceptor therapy
In radiopeptide therapy, the receptor specific peptides are used as highly
specific carriers to bring radionuclides directly to or into the cancer cells, so
that these cells will be killed by their radiation. Peptide analogues can be bound
to therapeutic radionuclides such as 177 Lu and 90 Y via chemical conjugators
(chelators). Of these, the somatostatin analogues of the octreotide class
have become the most fully established in clinical practice. Dosages are set
individually according to the pretherapeutic diagnosis, particularly in the case of
68 Ga labelled analogues.
The therapeutic substance is administered slowly as an intravenous infusion.
Within a few minutes after infusion, the radiopeptide docks at the receptor
sites and can stay there for some days, irradiating the tumour cells and thereby
destroying them. To avoid damage to the kidneys, through which the radioactive
therapeutic substance is cleared, these are washed through immediately before
and after the radionuclide injection with amino acid infusions. The therapy is
generally repeated after a lengthy interval [2.53–2.55].
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