Yttrium-90 and Rhenium-188 Radiopharmaceuticals for Radionuclide Therapy

2.3.1. Exploitation of certain metabolic properties of tumour tissue
2.3.1.1. Iodide and phosphate
The best example of exploiting metabolic properties is the treatment
of iodine accumulating thyroid tumours (as iodine metabolizing tissue) with
radioactive sodium iodide ( 131 I–NaI), which is currently the most common form
of metabolic tumour therapy with open radionuclides and has been in use since
the 1940s (see Section 2.4). Another example, rarely used, is the treatment of
malignant blood disorders (thrombocythaemia and polycythaemia vera). This
exploits the fact that 32 P accumulates in the bone marrow of such patients, owing
to an overproduction of certain blood cells, as the increased synthesis of nucleic
acids raises phosphate consumption.
2.3.1.2. Bone seeking radiopharmaceuticals
Examples of bone seeking products are the radiopharmaceuticals used for
palliative pain control in patients with skeletal metastases.
The substance previously applied for this was Na 2 H 32 PO 4 , and the
primary mechanism thought to underlie its action was the facilitated uptake of
radiophosphorous into the DNA and ribonucleic acid (RNA). However, the side
effects of the treatment raised concerns [2.17].
Following the identification of a series of radionuclides as bone seeking
isotopes by Hamilton [2.18], Pecher [2.19] reported a raised concentration of
strontium isotopes in the reactive zone of rapid bone growth around an osteogenic
sarcoma. The mechanism by which these radionuclides were incorporated in
ionic form was an ion exchange process involved in metabolism of the bone.
Key research leading to the introduction of 89 Sr to routine clinical practice was
performed by Firusian [2.20], who also demonstrated the superiority of this
method of treatment over 32 P therapy. Kutzner et al. [2.21] carried out a clinical
study on pain control using 90 Y citrate in patients with bone metastases from
primary prostate cancer. The main product to become established in clinical
practice was 153 Sm EDTMP, which becomes highly enriched in bone, particularly
at points of growth and in bone lesions. The EDTMP chelate is responsible
for the specific uptake into the newly formed bone matrix laid down by
osteoblasts [2.22, 2.23]. However, the bone affinity of the radioactive lanthanides
simply in ionic form has also been recognized for some time [2.24].
Although none of the 188 Re labelled bone pain palliation agents have yet
been commercialized, 188 Re HEDP has been applied clinically in cancer patients.
Here too, the ligand seems to play a more critical role in the incorporation process
than the radionuclide [2.8].
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