Theranostics is derived from a combination of the words “Therapy” and “Diagnostics”. These personalised nuclear medicine technologies are able to simultaneously or sequentially diagnose and treat cancer. Theranostics@AARO is a specialized clinic harnessing the capabilities of Theranostics in delivering cutting edge cancer treatment.
Our Theranostics Therapies
Liver Cancer Therapy
Liver Cancer Therapy- Yttrium-90 Selective Internal Radiation Therapy (SIRT)
Prostate Cancer Therapy
Prostate Cancer Therapy- Radium-223 Therapy (Xofigo)
- Lutetium-177 Prostate Specific Membrane Antigen (PSMA) Therapy
Neuroendocrine Cancer Therapy
Neuroendocrine Cancer Therapy- Lutetium-177 Octreotate Therapy
Radium-223 Therapy (Xofigo)
Radium 223 (Xofigo) is a radioactive pharmaceutical that is used to treat castrate resistant Prostate Cancer, symptomatic Bone
Metastases and no known Visceral Metastatic Disease.
How does Radium-223 Therapy (Xofigo) work?
Radium-223 (Xofigo) is an alpha-emitting radioisotope that mimics Calcium. When injected, Radium-223 will circulate through
the body and form complexes with bony mineral Hydroxyapatite at the areas of increased bony turnover, such as bone
metastases.
As such, Radium-223 (Xofigo) radioactivity can uniquely target areas of sclerotic bony metastases, causing DNA damage to the
cancer cells while relatively sparing normal bone due to the short radiation range.
What are the expected outcomes of Radium-223 Therapy (Xofigo)?
The aim of the therapy is to control the bony metastases and to reduce symptoms of bony pain (if present).
Radium-223 (Xofigo) therapy is a therapeutic agent that was shown to significantly extend overall survival in patients.
This was demonstrated in a double blind, randomised, placebo controlled phase III clinical trial of 921 patients with
castrate resistant Prostate Cancer with symptomatic bony metastases and no known visceral metastases (Alsympca
trial).
Following therapy, there is typically mild-moderate response in PSA levels (50% will have a drop of more that 30%),
while drop in ALP levels is typically more dramatic.
Lutetium-177 Prostate Specific Membrane Antigen (PSMA) Therapy
Lutetium-177 Prostate Specific Membrane Antigen Therapy (“Lu177 PSMA Therapy”) is a Nuclear Medicine
radionuclide treatment, allowing for very specific and targeted radiation therapy for Prostate Cancer. It is often used
for metastatic Castrate Resistant Prostate Cancer (mCRPC).
How does Lutetium-177 PSMA Therapy work?
Prostate Specific Membrane Antigen (PSMA) is a type II transmembrane glycoprotein that is found in concentrations
100-1000 times higher in Prostate cancers as compared with normal tissue.
PSMA is hence an excellent target for radionuclide imaging and therapy as it is highly expressed in prostate
cancers.
Small molecule PSMA ligands allow for rapid targeting of the Prostate Cancer cells. When these PSMA ligands are
bound with Lu177 radionuclides, they act as a “magic bullet” delivery system that allows for targeted radiotherapy of
Prostate Cancer cells.
What are the expected outcomes of Lu177 PSMA Therapy?
The aim of the therapy is to reduce tumour volume and stop the growth of cancer.
Lu177 PSMA therapy has proven anti-tumour activity and safety in the treatment of patients with metastatic
Castrate Resistant Prostate Cancer, and is an ideal therapeutic option for patients who do not tolerate
chemotherapy well or have extensive bone marrow involvement.
Lu177 PSMA therapies have shown trends towards Prostate Specific Antigen (PSA) reductions, lengthens overall
survival and progression free survival, with generally mild and transient toxicities.
Lutetium-177 Octreotate Therapy
Lutetium-177 Octreotate Therapy is a form of targeted or “magic bullet” cancer therapy, utilising Peptide molecules as carrier
agents to deliver tumoricidal radioisotopes to the target cancer tissue.
How does Lutetium-177 Octreotate Therapy work?
Lutetium-177 Octreotate Therapy relies on a unique nature of Neuroendocrine cancers, which are known to express Somatostatin
receptors at a much higher concentration as compared to normal cells.
Somatostatin is a naturally occurring peptide with various biological functions, that mediates its action through several
membrane-bound Somatostatin receptors. Currently, 5 subtypes of somatostatin receptors have been identified in humans
(SSRT1, SSRT2, SSRT3, SSRT4, SSRT5).
The distribution of various SSRT subtypes in human organ systems has been studied fairly extensively, and have also been found
in a large number of tumours. Neuroendocrine cancers are the archetypical class that have been extensively imaged and treated
using Somatostatin analogues, but other tumours such as Neuroblastomas, Meningiomas, Breast Cancers, Lymphomas, Renal
Cell Carcinomas, Hepatomas and Pheochromocytomas have been found to express Somatostatin receptors.
The principle of Somatostatin receptor targeting is based on linking a stable Somatostatin Analogue to a Radioisotope via a
chelating agent before administration into the patient, where uptake in the target tissue is dependent on SSRT mediated
internalisation of the Radioligand.
By using such radiolabelled Somatostatin Analogues, we are able to specifically target these cancer cells for both imaging and
treatment purposes.
What are the expected outcomes of Lutetium-177 Octreotate Therapy?
Lutetium-177 Octreotate therapy in the therapy of Neuroendocrine cancers has shown good clinical response (approximately
80%), with definite improved of survival outcomes and good safety profile.
A landmark study compared patients with well-differentiated, metastatic midgut Neuroendocrine tumours who either received
Lutetium-177 Octreotate therapy or long-term Octreotide injections.
It was found that Lutetium-177 Octreotate Therapy resulted in markedly longer progression free survival and significantly higher
response rate than just high dose injected Octreotide. An overall survival benefit was seen at interim analysis.
Yttrium-90 Selective Internal Radiation Therapy
Selective Internal Radiation Therapy (SIRT) is a form of Targeted Brachytherapy / Radiation Therapy developed to treat liver cancers. Sometimes referred to as radioembolisation, it
aims to target and destroy liver tumours.
How Does Yttrium-90 Selective Internal Radiation Therapy (SIRT) Work as a Liver Cancer Therapy?
The principle of brachytherapy involves delivering tumoricidal doses of radiation to the cancer but limiting quantities to normal adjacent tissue. Radiation is tumoricidal if sufficient
energy can be delivered to the target cells.
Targeted Internal Radiation Therapy offers super-selective therapy of tumours while effectively sparing normal liver parenchyma.
Simply put, small radioactive beads are targeted at a tumour through the patient’s blood vessels in the liver. These radioactive beads give off radiation over a limited, short distance, leaving the surrounding tissue unharmed.
The therapeutic basis of Microsphere Therapy is based on known vascular supply changes occurring in Hepatocarcinogenesis. Typically, liver parenchyma (functional tissue) is supplied mainly via the portal vein with a small supply from the hepatic artery.
In Hepatocellular Carcinoma and some Dysplastic nodules, this is reversed. Hepatic Arterial supply accounts for the majority of vascular supply (approximately 80%), and blood flow is preferentially distributed to the tumour relative to normal liver parenchyma. Meaning that a patient suffering from HCC has a majority of their blood flow being supplied to the
tumour as opposed to the functional tissue of the liver.
Yttrium-90 microspheres, when given, will preferentially flow to the tumour because of the increased Arterial Vascular supply. The diameter of SIR-Spheres enables them to become implanted in the tumour microvasculature. However, they are too large to pass through the end arterioles into the hepatic sinusoids, which have a restrictive diameter of 8-10 micron.
This preferential stasis of microspheres within the tumour bed coupled with the limited range and high-energy emission of the Yttrium-90 allows a high tumour radiation dosage with
little exposure to surrounding liver parenchyma in theory.
WHAT ARE THE EXPECTED OUTCOMES OF SIRT?
SIRT is generally a safe and effective liver cancer therapy, with no immediate side effects expected.
Outcomes depend on the team’s experience and are generally better in tertiary institutions with multidisciplinary expertise.
The reported survival benefits are similar to that of oral Sorafenib treatment, which has been considered the standard of care for patients with advanced Unresectable Hepatocellular Carcinomas – where other treatment options have proven ineffective.
However, there are better quality of life scores reported, lower side effects and improved progression, free survival and time to tumour progression.
