Yttrium-90 and Rhenium-188 Radiopharmaceuticals for Radionuclide Therapy

adioiodine labelled anti-NCAM antibody ERIC1 seems to be a promising radiopharmaceutical
for treatment of neuroblastoma. The optimal dose is 1–2 MBq/animal. This would correspond
to ~600–1200 MBq in humans (for a child of 15 kg).
Initial experiments with 90 Y labelled ERIC1 have been very promising. These antibodies
showed an unequivocal therapeutic effect, whereas 131 I MIBG had no influence on tumour
growth, even when much higher radioactivity was injected per animal. Studies planned for
the future include improved dose finding studies, fractionation of radiation dose realized by
intravenous application of radiolabelled ERIC1, investigation of other radioimmunoconstructs
directed against NCAM and investigation of other tumour types with NCAM on tumour cells
and pretargeting.
5.1. EXPERIMENTS
5.1.1. Yttrium-90 or 111 In labelled rituximab
5.1.1.1. Introduction
The introduction of MAbs such as rituximab in recent years has brought
about decisive progress in the treatment of aggressive and indolent NHL [5.1].
Since then, a number of antibodies have been developed for use in oncological
disorders. Further improvement to the unmodified antibody has been its coupling
to β emitters such as 131 I and 90 Y. The aim here was to establish the biodistribution
of labelled chimeric antibody rituximab and to determine whether 111 In is a
suitable surrogate for 90 Y.
5.1.1.2. Methods
The antibody against NHL can be acquired commercially. The labelling
of rituximab to 90 Y first involves a non-radioactive modification of the
antibody to allow chemical binding with 90 Y. This is achieved by the coupling
of isothiocyanatobenzylDOTA (NCS-Bz-DOTA) to rituximab. The DOTA
rituximab conjugate solution can subsequently be lyophilized to allow interim
storage until labelling with the corresponding radionuclide.
The 111 In labelling for pretherapeutic dosimetry, the 90 Y labelling for
therapeutic purposes and the quality control procedures were carried out under
clean room conditions. Quality control of the radiopharmaceutical was carried
out by size exclusion high performance liquid chromatography (HPLC). The
final filtration and bottling were done under sterile conditions. The ready to use
solutions should have an activity concentration of ~185 MBq (5 mCi) 111 In for
dosimetry and ~740 MBq (20 mCi) 90 Y for therapeutic purposes, each in a volume
of 3 mL.
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