12 July 2023
Check Up #15 - What is therapeutic Nuclear Medicine
“Molecular Radiotherapy”?
In CheckUp #14, we talked about the different types of cancer treatments with ionizing radiation: internal and external radiotherapies. We promised we would return to this subject to talk in more detail about a special type of internal radiotherapy: molecular radiotherapy. This activity is integrated in Nuclear Medicine, a medical specialty that, in Oncology, uses radiopharmaceuticals to diagnose, treat, and evaluate the response of cancers to existing or new drugs.
Molecular Radiotherapy is also known as Targeted Radionuclide Therapy and, in its more specific form, as Peptide Receptor Radionuclide Therapy. It is performed primarily using two techniques: the administration of radiopharmaceuticals (with no clinically measurable pharmacological action) and radioparticles – that is, substances that have been attached to an ionizing radiation-emitting element, or radionuclide, before being administered to the patient. This binding persists after administration.
The second option is the most recent one. It consists of embedding a radionuclide in microparticles made of glass, resin, or a biodegradable polymer composed of lactic acid molecules. In the first option, which is also the most common, a radionuclide is attached to a drug or biological analog to form a radiopharmaceutical. This same principle is also used in nuclear medicine imaging for diagnosis, staging, and follow-up of patients after treatment (see CheckUp #11).
As already mentioned in CheckUp #14, there is yet another type of internal radiation therapy: brachytherapy. But unlike brachytherapy, which uses "sealed" radioactive sources (in solid form) that are administered at a single anatomical site, nuclear radiotherapy uses unsealed ("liquid" or encapsulated) radioactive sources for systemic administration (injectable or oral).
At the Champalimaud Foundation's Nuclear Medicine-Radiopharmacology Service, patients with neuroendocrine tumours are being treated with molecular radiotherapy, usually in four sessions every eight weeks or so. Soon, this service will begin treating patients with metastatic prostate carcinomas that are resistant to chemical castration. Today, it already treats patients with bone metastasis from chemical castration-resistant carcinomas of the prostate, in six therapy sessions at four-week intervals.
These treatments do not require hospitalising the patient for longer than six or eight hours. Only in cases in which the therapy involves Iodine-131 may a stay of more than 24 hours in the clinic, with specific radiological protection, be necessary.
The Nuclear Medicine-Radiopharmacology Service also carries out a type of treatment in which the radioactive sources are administered at the site affected by the disease. In particular, glass microparticles loaded with the radionuclide Yttrium-90 (Y-90) are used to treat patients with liver tumours, both primary (hepatocarcinoma) and metastatic (cholangiocarcinoma, thymoma, colorectal, etc.). This treatment, known as Selective Internal Radiation Therapy or, in short, radioembolization of the liver, consists in the administration of millions of microspheres by catheterization of the hepatic artery, or one of its branches, with the catheter usually being introduced via the femoral artery.
The term radioembolization (radio + embolization) very well describes the two ways in which the treatment acts on the liver: by radiation at the site of the tumours, sparing the normal liver tissue as much as possible; and by embolization (obstruction) of the hepatic pathways (arteries) leading to the tumour, which reduces its irrigation and the consequent supply of "food" to the tumour. These treatments are usually performed in a single session, and the patient may need to be hospitalized, but generally never for more than a day.
In both techniques (systemic administration of specific radiopharmaceuticals or microparticles to the tumour site), the measurement of the ionizing radiation dose is customised for each patient.
In this era of personalised medicine, in which each patient's malignant tumours can be characterized by the presence of specific molecules on their cells, it is already possible to apply tumour-targeted radionuclide therapy by tailoring the active molecule to the type of malignant tumour. This allows for the personalised systemic treatment of each patient's specific cancer. On the other hand, technological advances in imaging equipment with radiopharmaceuticals and radioparticles, together with the improvement in the ability to catheterise organs and their segments – as in the case of hepatic radioembolization – also improve the selectivity needed to personalise this type of local treatment.
