Radio-theranostics: How Precision Medicine using tiny Radioactive Molecules are Personalising Cancer Care

By: Dr. Ishita B Sen, Senior Director - Nuclear Medicine Fortis Memorial Research Institute, Gurugram

The term 'theranostics' is an integration of the words 'therapeutics' and 'diagnostics.' Theranostic agents are paired agents, one an imaging agent that 'sees' the lesion and the other, a companion therapeutic agent that treats the same lesions. While the concept of theranostics is widely used in various molecular probes in oncology, the most relevant application of theranostics is in nuclear medicine where it is called Radiotheranostics. Paired radionuclides attached to a common probe are used first for imaging the tumour with a specific PET scan and then treating the same using a therapeutic radionuclide attached to the same probe. This strategy is aligned to the concept of personalised precision medicine, which leads to enhanced therapy efficacy, manageable adverse events, improved patient outcome and lower overall costs.

The Department of Nuclear Medicine at the Fortis Memorial Research Institute (FMRI), Gurugram, has been one of the apex centres in the country practising Radio-theranostics since 2 0 1 3 . Prostate cancer , neuroendocrine tumours and thyroid

cancers are the most common tumours being treated by Radiotheranostics. The Ga68 PSMA scan, which is a highly specific PET scan for prostate cancer, is increasingly becoming the standard of care for the staging of prostate cancer. The radioactive tracer (68Ga-PSMA-11) attaches to PSMA proteins which are overexpressed in prostate cancer cells, both within the prostate gland and in the metastatic sites. The PSMA PET scan thus pinpoints the location of the tumour within the prostate gland and accurately stages the disease by identifying all the metastatic sites beyond the prostate gland where the cancer may reside. This allows the surgeon, the Radiation On c o l o g ist a n d t h e Me d i c a l Oncologist to correctly strategise which patient gains by local therapy like surgery or definitive radiotherapy and which needs systemic therapy like chemotherapy. Lu177 PSMA, a therapeutic radio-theranostics agent, is then used to treat metastatic prostate cancers, especially those that are refractory to systemic hormonal therapy or chemotherapy. Treatment with these radio-theranostics agents not only improves survival in these patients of advanced prostate cancer but also significantly improves their quality of life. At the Nuclear Medicine Centre at FMRI, more than a thousand treatments have been carried out in prostate cancer patients over the last eight years.

Another tumour where radiotheranostics is often used is in well differentiated neuroendocrine tumours. Patients of neuroendocrine tumour often have advanced disease at presentation with the liver often being extensively involved in the metastatic process. Delivering cytotoxic levels of radiation without damaging the surrounding normal tissue is often the challenge in these pa ti ents. Ga 6 8 DOTANOC, a diagnostic radio-theranostic agent, identifies the somatostatin receptors which are overexpressed in these tumours. Lu177 DOTANOC therapy, als o called PRRT (Peptide radionuclide therapy) a therapeutic radiopharmaceutical, then seeks out these somatostatin receptors on the tumours, attaches to the receptors and delivers a high payload of radiation to the tumours. Since the penetration of the ionising radiation in tissue is only few micrometres, the surrounding normal tissue is spared. PRRT is also used in the treatment of meningiomas and paragangliomas, which also express the somatostatin receptors. Sometimes, PRRT is combined with highly targeted stereotactic external radiotherapy to deliver combined internal and external radiotherapy to deliver a double whammy of damaging radiation to the tumour cells While traditionally, the therapeutic theranostic agents used beta radiation emitting tracers like lutetium, in the past few years, alpha emitting radionuclides like Ac225 (Actinium 225) and Bi213 (Bismuth 213) have opened up an entirely new era in nuclear theranostics. Alpha emitting radionuclides deliver up to 20 times higher cytotoxic radiation dose to the tumours. And since the penetration of these alpha rays in tissue is manifold less than the beta emitting radionuclides, the damage to surrounding tissue is far less. Often called the magic bullet therapy, targeted alpha therapy is changing the paradigm of radio-theranostics. The Nuclear Medicine Department at FMRI was the first centre in the entire South-east Asia to start performing targeted alpha radiation therapy