What Is Radioligand Therapy?
Radioligand therapy (RLT) is a form of targeted cancer treatment that uses radioactive molecules to deliver radiation directly to tumour cells. The “ligand” part of the name refers to a molecule that binds to a specific receptor on the cancer cell surface. When that ligand is attached to a therapeutic radioactive isotope, it carries the radiation straight to the tumour while sparing most healthy tissue.
This targeted approach is fundamentally different from external beam radiation, where radiation is delivered from outside the body through the skin. With radioligand therapy, the radiation source travels through the bloodstream and homes in on cancer cells wherever they are in the body, including metastatic sites that would be difficult or impossible to treat with external radiation alone.
Radioligand therapy is closely linked to the concept of radioligand theranostics, where a diagnostic scan first identifies whether the patient’s cancer expresses the target receptor, and then a therapeutic version of the same molecule is used for treatment.
Types of Radioligand Therapy Available
Several forms of radioligand therapy are now accessible to patients in Bangalore, each targeting a different type of cancer through a specific receptor system.
Lu-177 PSMA Therapy for Prostate Cancer
PSMA (prostate-specific membrane antigen) is a protein found on the surface of prostate cancer cells, often in high concentrations. Lu-177 PSMA therapy involves injecting a radioactive molecule that binds to PSMA, delivering beta radiation directly to prostate cancer cells throughout the body.
This therapy is primarily used in patients with metastatic castration-resistant prostate cancer (mCRPC) who have already undergone other lines of treatment, including hormonal therapy and chemotherapy. A PSMA PET CT scan is performed first to confirm that the cancer expresses enough PSMA for the therapy to be effective.
The landmark VISION trial demonstrated that Lu-177 PSMA therapy improved overall survival and progression-free survival in this patient population, and it has since become an established part of the treatment options for advanced prostate cancer.
Lu-177 DOTATATE Therapy for Neuroendocrine Tumours
Neuroendocrine tumours (NETs) are a group of cancers that arise from hormone-producing cells in various organs, most commonly the gastrointestinal tract and pancreas. Many NETs express somatostatin receptors on their surface.
Lu-177 DOTATATE (also known by its brand name Lutathera) binds to somatostatin receptors and delivers targeted radiation to NET cells. It is used primarily for well-differentiated, somatostatin receptor-positive gastroenteropancreatic NETs that are inoperable or metastatic. A Ga-68 DOTATATE PET CT scan confirms receptor expression before treatment begins.
The NETTER-1 trial showed significant improvements in progression-free survival for patients treated with Lu-177 DOTATATE compared to high-dose octreotide alone.
Lu-177 FAPI Therapy
FAPI-targeted radioligand therapy is a newer development that targets fibroblast activation protein in the tumour microenvironment. While still considered investigational for many cancer types, early clinical data from various centres have shown responses in cancers that lack other targeted treatment options, including certain sarcomas, pancreatic cancers, and other solid tumours.
A FAPI PET CT scan is used to assess whether a patient’s cancer shows sufficient tracer uptake to warrant therapy. This remains an evolving area, and treatment availability may depend on institutional protocols and ongoing research.
Who Qualifies for Radioligand Therapy?
Not every cancer patient is a candidate for radioligand therapy. Several criteria must be met:
- Receptor expression: The cancer must express the target receptor at a level high enough for the therapy to work. This is determined by a diagnostic PET CT scan (PSMA PET for prostate cancer, DOTATATE PET for NETs, FAPI PET for FAP-expressing tumours).
- Prior treatment history: For approved indications like Lu-177 PSMA in prostate cancer, therapy is typically offered after other standard treatments have been tried. For NETs, it may be used earlier in the treatment sequence.
- Adequate organ function: Patients need sufficient kidney function, bone marrow reserve, and liver function to safely undergo treatment. Blood tests are performed to assess this before each cycle.
- Performance status: The patient should be well enough to tolerate the treatment and the required observation period. Very frail patients may not benefit.
The decision is made by a multidisciplinary team that typically includes a medical oncologist, nuclear medicine physician, and sometimes a radiation oncologist.
How to Get Referred
The referral process for radioligand therapy generally follows this path:
Step 1: Your treating oncologist identifies radioligand therapy as a potential option based on your cancer type and treatment history.
Step 2: A theranostic PET CT scan is ordered to confirm receptor expression. This scan is the gatekeeper; without adequate receptor expression, radioligand therapy will not be effective.
Step 3: If the scan is positive, your oncologist refers you to a nuclear medicine centre that offers radioligand therapy. Alternatively, you or your doctor can contact us directly to discuss whether radioligand therapy is appropriate for your situation.
Step 4: The nuclear medicine team reviews your complete medical history, imaging, and blood work to confirm eligibility and plan the treatment schedule.
What the Treatment Process Involves
Radioligand therapy is administered as an intravenous infusion, similar in concept to a chemotherapy session but with important differences.
Pre-treatment assessment: Blood tests, review of recent imaging, and a clinical evaluation are completed before each cycle.
Infusion day: The radioligand is infused slowly over 20 to 30 minutes. For Lu-177 DOTATATE, an amino acid infusion is given alongside the treatment to protect the kidneys. The total time in the treatment area is usually four to six hours, including observation.
Post-infusion monitoring: After the infusion, you may undergo a post-therapy scan to confirm that the radioligand has distributed to the tumour sites as expected. You will also receive instructions on radiation safety precautions for the first few days after treatment, as your body will emit low levels of radiation while the isotope decays.
Cycle schedule: Most radioligand therapies are given in cycles, typically four to six cycles spaced six to eight weeks apart. The exact schedule depends on the specific therapy and your individual response.
Follow-up: Blood tests are performed between cycles to monitor kidney function, liver function, and blood counts. Follow-up imaging, usually a PET CT scan, is done after two to three cycles to assess treatment response.
Side Effects
Radioligand therapy is generally well tolerated compared to chemotherapy, but side effects can occur:
- Fatigue is the most common complaint and usually resolves within a week or two after each cycle
- Nausea can occur on the day of treatment, particularly with DOTATATE therapy, and is managed with anti-nausea medication
- Dry mouth (xerostomia) can develop with PSMA therapy, as salivary glands express some PSMA
- Bone marrow suppression, including lowered blood counts, can occur and is monitored with regular blood tests
- Kidney effects are monitored, and protective measures (amino acid infusion, dose adjustments) are used to minimise risk
Your nuclear medicine physician will discuss the specific risk profile for the type of radioligand therapy recommended for you.
Taking the Next Step
If you or a family member has been diagnosed with metastatic prostate cancer, neuroendocrine tumours, or another cancer type where radioligand therapy may apply, the first step is a conversation with your oncologist about whether a theranostic PET CT scan is appropriate. That scan determines eligibility and sets the path forward.
For questions about radioligand theranostics or to discuss a specific case, you can contact us to connect with the nuclear medicine team.