Radioligand Therapy Explained: Lu-177 PSMA, Lu-177 DOTATATE and Nuclear Medicine for Cancer

Last medically reviewed: October 2026

Radioligand therapy is a type of targeted cancer treatment that uses a radioactive medicine to deliver radiation to cancer cells throughout the body. It combines a molecule that recognises a particular cancer-associated target with a radioactive isotope that damages the targeted cells.

Two important examples are lutetium-177 PSMA therapy, used for selected patients with prostate cancer, and lutetium-177 DOTATATE therapy, used for selected patients with neuroendocrine tumours.

Unlike external-beam radiotherapy, which directs radiation towards a selected area from outside the body, radioligand therapy travels through the bloodstream to reach cancer sites that express the appropriate target.

However, this treatment is not suitable for every patient or every cancer. The cancer must have the appropriate biological target, the patient's overall condition must be considered, and the potential benefits must be weighed against the risks.

This guide explains the science, patient selection, treatment process, benefits, limitations and safety considerations in plain English. It is for education and does not replace advice from an oncologist or nuclear medicine specialist.

The essentials at a glance

Lu-177 PSMA: targets prostate-specific membrane antigen (PSMA) on prostate cancer cells. Pluvicto is a commonly used treatment brand.
Lu-177 DOTATATE: targets somatostatin receptors on certain neuroendocrine tumour cells. Lutathera is a commonly used treatment brand.
A special scan comes first: molecular imaging helps determine whether the cancer expresses the target.
Treatment is given intravenously: patients receive a radioactive medicine through a vein, usually in several treatment cycles.
Targeted does not mean risk-free: bone marrow, kidneys and other normal tissues may also be exposed to radiation.
The goal is generally disease control: in advanced cancer, treatment may shrink tumours, slow progression or relieve symptoms, but it does not guarantee a cure.

1. What is radioligand therapy?

Radioligand therapy (RLT), also known more broadly as radiopharmaceutical therapy, is a form of precision cancer treatment. It delivers a radioactive substance to cancer cells using a targeting molecule called a ligand.

Think of the treatment as a delivery system with two components:

The targeting molecule: recognises a particular protein or receptor associated with the cancer.
The radioactive payload: releases energy that damages the DNA of targeted cells and can lead to their death.

After the radiopharmaceutical is injected into a vein, it circulates through the body. The targeting molecule binds preferentially to cells expressing the relevant target. The radioactive isotope then delivers radiation over a short distance around those cells.

Lutetium-177 emits beta particles that produce the main therapeutic effect. It also emits gamma radiation that can be detected for imaging and treatment assessment.

Radiation may damage neighbouring tumour cells as well as the cells that bind the drug. This is sometimes called a cross-fire effect. The extent of tumour coverage depends on the distribution of the targeting molecule, the tumour's biology and other treatment factors.

How is it different from conventional radiotherapy?

Treatment	How it delivers treatment	Potential role
External-beam radiotherapy	Radiation is directed at a defined area from outside the body.	Treating selected tumours or controlling symptoms at particular sites.
Chemotherapy	Medicines circulate through the body and act through their particular anticancer mechanisms.	Treating cancer throughout the body, depending on the drug and cancer type.
Radioligand therapy	A radioactive medicine circulates through the body and preferentially accumulates at cells expressing its target.	Treating selected cancers at multiple sites when the relevant molecular target is present.

These treatments are not necessarily alternatives to one another. Depending on the cancer, stage and previous treatment, radioligand therapy may be used before, after or alongside other treatments as part of a specialist treatment plan.

2. The two major examples: Lu-177 PSMA vs Lu-177 DOTATATE

Both treatments use the radioactive isotope lutetium-177, but their targeting molecules and clinical uses are different. They should not be considered interchangeable.

A. Lu-177 PSMA therapy: for selected prostate cancers

Common treatment brand: Pluvicto (lutetium Lu-177 vipivotide tetraxetan).

Target: Prostate-specific membrane antigen, or PSMA.

Typical cancer setting: PSMA-positive metastatic prostate cancer in patients who meet the applicable treatment criteria.

PSMA is a protein found at high levels on many prostate cancer cells. The radioligand is designed to bind to PSMA and deliver radiation near the cancer cells.

Before treatment, a PSMA PET scan is generally used to determine whether the cancer demonstrates sufficient uptake of the imaging tracer. A scan is essential because not all prostate cancers express PSMA at the same level.

Potential treatment goals include:

Slowing cancer progression.
Reducing the size or activity of some tumours.
Controlling disease that has spread to bones, lymph nodes or other organs.
Maintaining quality of life while controlling advanced disease.

Eligibility depends on the cancer's characteristics, disease stage, previous and planned treatments, scan findings, kidney function, blood counts and overall clinical condition.

B. Lu-177 DOTATATE therapy: for selected neuroendocrine tumours

Common treatment brand: Lutathera (lutetium Lu-177 dotatate).

Target: Somatostatin receptors, particularly receptors expressed by many well-differentiated neuroendocrine tumours.

Typical cancer setting: Somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumours (GEP-NETs).

Neuroendocrine tumours, or NETs, can arise in organs such as the stomach, small intestine, rectum and pancreas. Many NET cells express somatostatin receptors on their surfaces.

DOTATATE is a peptide designed to bind to these receptors. When labelled with lutetium-177, it can deliver radiation to receptor-positive tumour cells.

Patients usually undergo somatostatin receptor imaging, such as a gallium-68 DOTATATE PET scan or another appropriate receptor-based scan, to assess whether their tumours are likely to take up the treatment.

Lu-177 DOTATATE treatment is also known as peptide receptor radionuclide therapy (PRRT).

Potential treatment goals include:

Slowing tumour growth.
Reducing tumour burden in some patients.
Controlling disease that has spread beyond the original tumour.
Helping control selected symptoms associated with NETs.

Not every neuroendocrine tumour is suitable. Tumour grade, differentiation, receptor expression, disease distribution, kidney function, bone marrow reserve and previous treatments all matter.

Comparison table: the important differences

Feature	Lu-177 PSMA	Lu-177 DOTATATE
Common brand	Pluvicto	Lutathera
Target	PSMA	Somatostatin receptors
Main cancer type	Prostate cancer	Selected gastroenteropancreatic NETs
Typical selection scan	PSMA PET	Somatostatin receptor PET
Common US treatment schedule	Every 6 weeks, up to 6 doses for the relevant indications	Every 8 weeks, usually 4 doses
Important safety concerns	Blood count suppression, kidney toxicity and radiation exposure	Blood count suppression, kidney toxicity, gastrointestinal effects and long-term marrow risks

The schedules above reflect common US prescribing regimens, not a recommendation for an individual patient. Treatment protocols, licensed indications and practical arrangements can differ by country and clinical circumstances.

3. How does radioligand therapy find cancer?

Radioligand therapy depends on a biological feature of the tumour. The treatment does not simply recognise the organ where the cancer began; it relies on a specific molecular target.

Step 1: Identify the molecular target

The medical team assesses the cancer diagnosis, pathology report, disease stage, previous treatments and available imaging. A tumour must express the relevant target for the corresponding radioligand to have a reasonable chance of working.

Step 2: Perform a molecular imaging scan

For prostate cancer, the patient may undergo PSMA PET/CT. For eligible neuroendocrine tumours, the patient may undergo somatostatin receptor PET/CT or another appropriate scan.

These imaging tests use a diagnostic radioactive tracer that attaches to the target. A PET scanner then displays where the tracer accumulates.

The scan helps the team assess:

Whether the cancer shows the required target expression.
Where the disease is located.
Whether some lesions appear less likely to respond because they show little or no tracer uptake.
Whether the findings fit the patient's diagnosis and overall treatment plan.

Step 3: Assess treatment suitability

A positive scan does not automatically mean that treatment is safe or appropriate. The medical team also considers blood counts, kidney function, liver function, symptoms, other medicines, prior treatment toxicity and the patient's general health.

Step 4: Administer the radioactive treatment

The treatment is given intravenously in a specialist nuclear medicine or radiopharmaceutical therapy service. The radioactive medicine circulates and preferentially binds to the targeted cells.

Step 5: Monitor response and safety

Doctors monitor blood counts, kidney function, symptoms and other relevant tests. Follow-up imaging and disease-specific markers may be used to determine whether treatment is controlling the cancer.

An important limitation: cancer can be biologically heterogeneous. One tumour deposit may express abundant target while another has low expression. That is one reason a positive scan cannot guarantee that every cancer site will respond.

4. Who may be eligible?

Eligibility depends on the particular radioligand, the approved indication, the cancer's molecular features and the patient's clinical condition.

Potential candidates for Lu-177 PSMA

Depending on the country and approved indication, a candidate may have:

Prostate cancer that is metastatic and demonstrates PSMA uptake on an appropriate PET scan.
Disease that meets the relevant treatment-stage and prior-treatment criteria.
Blood counts and kidney function that are acceptable for treatment.
An overall clinical condition that allows the treatment to be delivered safely.

2026 US regulatory update: On July 31, 2026, the US FDA approved Pluvicto in combination with androgen receptor pathway inhibitor (ARPI) therapy for selected adults with PSMA-positive metastatic hormone-sensitive prostate cancer. Its existing US indication also covers selected patients with metastatic prostate cancer that has progressed despite androgen pathway treatment, including those considered appropriate to delay taxane chemotherapy or who have received previous taxane-based chemotherapy.

The evidence and treatment requirements are not identical across these settings. In the PSMAddition trial supporting the 2026 approval, adding Pluvicto to an ARPI significantly improved radiographic progression-free survival compared with an ARPI alone. At the FDA's reported analysis, median radiographic progression-free survival had not been reached in either group, and overall survival data were immature. This does not establish the magnitude of an overall-survival benefit in that particular analysis.

These are US approvals. Patients in other countries should ask their oncology team which indications are locally licensed and accessible.

Potential candidates for Lu-177 DOTATATE

Patients may be considered when they have a suitable neuroendocrine tumour with sufficient somatostatin receptor expression and meet the applicable clinical criteria.

The US-approved Lutathera indication covers somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumours, including tumours arising in the foregut, midgut and hindgut. Other neuroendocrine tumours and other radioligands may have different evidence and regulatory status.

When might treatment not be suitable?

Treatment may be inappropriate or require additional evaluation when:

The required molecular target is absent or insufficiently expressed.
Important tumour sites show little uptake and are unlikely to be adequately targeted.
Kidney function is severely impaired or blood counts are too low.
The patient has significant competing medical problems or poor general condition.
Pregnancy, fertility concerns or other safety considerations require special management.
Another treatment is more appropriate for the cancer's current stage or biology.

These are considerations for specialist review, not a complete list of contraindications or automatic reasons to exclude treatment.

5. What happens during treatment?

Radioligand therapy is usually delivered in repeated treatment cycles rather than as a single injection. The exact process depends on the medicine, the treatment centre and the patient's needs.

Before the first treatment

The team generally reviews the diagnosis, imaging, previous treatments, current medicines and relevant laboratory tests. Patients may be asked to undergo a recent blood test and assessment of kidney function.

Discuss the following with the team before the appointment:

All prescription medicines, non-prescription products and supplements.
Previous radiotherapy, chemotherapy or radionuclide treatments.
Kidney disease, blood disorders or previous serious treatment toxicity.
Pregnancy, breastfeeding or future fertility plans, where relevant.
Travel arrangements, home support and any difficulties following radiation precautions.

During Lu-177 PSMA therapy

The radiopharmaceutical is administered through a vein. The clinical team observes the patient according to the treatment protocol and provides instructions on hydration, urination and radiation safety.

For the relevant US indications, the commonly prescribed regimen is administration every six weeks for up to six doses, subject to disease status, tolerance and the prescribing plan.

During Lu-177 DOTATATE therapy

Lutathera treatment requires additional supportive measures. An intravenous amino acid solution is used to help reduce radiation exposure to the kidneys, and anti-nausea medication is commonly given because the amino acid infusion can cause nausea or vomiting.

The usual US regimen is four doses approximately eight weeks apart. The team may also coordinate the timing of long-acting or short-acting somatostatin analogues, such as octreotide, according to the treatment protocol.

After each treatment

The treatment team will explain when to return for blood tests, kidney monitoring and other assessments. Depending on the radiopharmaceutical, radiation measurements and local regulations, some patients may require specific arrangements before leaving the treatment facility.

Follow the treating centre's written radiation safety instructions. They should explain how long to limit close contact with others, particularly young children and pregnant people, and what to do about toilet hygiene, hydration, travel and sleeping arrangements.

6. Side effects and long-term risks

Radioligand therapy can be more selective than some forms of systemic treatment, but it is not completely specific to cancer cells. Normal tissues may also take up the medicine or be exposed to radiation circulating in the body.

Side effects differ between Lu-177 PSMA and Lu-177 DOTATATE. They also depend on the dose, previous treatments, blood counts, kidney function and other individual factors.

Potential side effects of Lu-177 PSMA

Fatigue: tiredness can occur during treatment.
Dry mouth: PSMA-targeting compounds may accumulate in salivary and lacrimal glands.
Nausea and reduced appetite: these symptoms may occur during or after treatment.
Blood count changes: the treatment can reduce red blood cells, white blood cells or platelets.
Kidney toxicity: kidney function needs appropriate monitoring.
Radiation exposure: the patient must follow the safety instructions provided by the treatment centre.

More serious complications can occur. Severe infection related to low white blood cells, significant anaemia, bleeding related to low platelets or kidney injury need prompt medical assessment.

Potential side effects of Lu-177 DOTATATE

Nausea and vomiting: these can be related to treatment and the accompanying amino acid infusion.
Fatigue: patients may feel unusually tired.
Reduced blood counts: anaemia, low white blood cells or low platelets may develop.
Kidney toxicity: kidney function is monitored, and protective amino acid infusion is used.
Liver-related laboratory changes: some patients develop changes in liver blood tests.
Hormonal or hypersensitivity reactions: uncommon but potentially serious reactions need specialist monitoring.

Long-term risks include the possibility of myelodysplastic syndrome (MDS), acute leukaemia or persistent bone marrow problems. These complications are uncommon but important, particularly for patients whose bone marrow has already been exposed to previous cancer treatments.

What about fertility and pregnancy?

Radioligand therapy may cause harm to an unborn child and may affect fertility. Pregnancy status, contraception and fertility preservation should be discussed with the treatment team before therapy when relevant.

Patients should obtain medicine-specific advice on the duration of contraception, whether breastfeeding must be stopped, and whether sperm or egg preservation should be considered. The recommendations depend on the particular treatment and individual circumstances.

When should patients seek urgent medical advice?

Contact the treatment team promptly if you develop a fever, shaking chills, unusual bleeding, unexplained bruising, persistent vomiting, markedly reduced urine output, or symptoms that are worsening rather than improving.

Seek emergency medical attention for severe breathlessness, collapse, a severe allergic reaction or other potentially life-threatening symptoms. Follow any emergency contact instructions issued by the treating centre.

7. Does radioligand therapy cure cancer?

Radioligand therapy can produce meaningful benefits, but its purpose and likely outcome depend on the cancer type, stage, molecular target, prior treatment and the individual's health.

In advanced prostate cancer and metastatic neuroendocrine tumours, treatment is often intended to control the disease, delay progression and potentially improve symptoms or quality of life. Some patients experience substantial tumour responses, while others have limited benefit or develop resistance.

It is important to distinguish three different outcomes:

Tumour response: measurable cancer deposits shrink or show reduced activity.
Disease control: the cancer remains stable or progresses more slowly.
Overall survival benefit: patients live longer compared with an appropriate control group in a clinical study.

These outcomes are related but are not interchangeable. A scan showing tumour shrinkage does not automatically prove that a treatment extends survival, and a study showing delayed progression does not guarantee a particular outcome for an individual patient.

Clinical trials provide the best way to assess these benefits. Results should be interpreted in the context of the patients studied, the comparison treatment, the length of follow-up and whether the results apply to the patient's own disease setting.

8. How does radioligand therapy compare with other cancer treatments?

There is no universally best cancer treatment. The appropriate choice depends on cancer biology, stage, treatment goals, previous therapies, patient preferences and the strength of the available evidence.

Approach	Main principle	Important limitation
Radioligand therapy	Delivers radiation through a molecule that binds to a tumour-associated target.	Requires an appropriate target; normal tissues can still be exposed.
Chemotherapy	Uses drugs that kill cancer cells or interfere with their growth.	Effects on healthy tissues can cause significant adverse reactions.
Immunotherapy	Helps the immune system recognise or attack cancer, depending on the treatment.	Only some cancers and patients benefit; immune-related toxicities can occur.
Targeted drug therapy	Acts on a particular molecular pathway or alteration.	Requires the relevant biological feature, and resistance may develop.
External-beam radiotherapy	Directs radiation at a specific anatomical area.	Treating widespread disease may require other systemic approaches as well.

Radioligand therapy does not automatically replace chemotherapy, hormone treatment, surgery, immunotherapy or external-beam radiotherapy. In some situations it is used after other treatments; in others, it may be considered earlier. The recommended sequence depends on the disease and the applicable evidence and approvals.

9. What does the evidence tell us?

Radioligand therapy is an established treatment approach for selected cancers, but the evidence must be assessed separately for each drug and disease setting.

Evidence for Lu-177 PSMA

Clinical trials have demonstrated important benefits in selected patients with PSMA-positive metastatic prostate cancer. Evidence includes studies of disease progression and survival, with results depending on the treatment setting and comparison group.

The 2025 US FDA expansion for selected patients with metastatic castration-resistant prostate cancer was supported by the PSMAfore trial. In that study, median radiographic progression-free survival was 9.3 months with Lu-177 PSMA-617 compared with 5.6 months with a change in androgen receptor pathway inhibitor therapy. The reported hazard ratio was 0.41. Overall survival was not statistically significantly different in the reported analysis, which was affected by treatment crossover.

In July 2026, the US FDA also approved Pluvicto with an androgen receptor pathway inhibitor for selected patients with PSMA-positive metastatic hormone-sensitive prostate cancer. This approval was supported by PSMAddition, which demonstrated improved radiographic progression-free survival. Overall survival data were immature at the FDA's reported analysis.

These results support the use of the treatment in the populations studied. They should not be interpreted as identical benefits for every patient, every disease stage or every treatment combination.

Evidence for Lu-177 DOTATATE

The NETTER-1 trial provided pivotal evidence for Lu-177 DOTATATE in patients with advanced, progressive, somatostatin receptor-positive midgut neuroendocrine tumours. Subsequent evidence and regulatory indications support its use in broader groups of appropriate gastroenteropancreatic neuroendocrine tumours.

However, neuroendocrine tumours are a diverse group of cancers. Tumour differentiation, grade, primary site, receptor expression and disease behaviour matter when deciding whether PRRT is appropriate.

Questions to ask when reviewing the evidence

When someone recommends radioligand therapy, patients can ask:

Was the treatment studied in patients with my cancer type, stage and molecular profile?
What was the comparison treatment in the clinical trial?
Did the trial demonstrate improved survival, delayed progression, symptom improvement or another outcome?
What proportion of patients experienced serious adverse reactions?
How long were patients followed, and what remains uncertain?
Are the published results applicable to my previous treatments and overall health?

A credible explanation should distinguish established clinical benefits from early research, theoretical possibilities and results that remain uncertain.

10. Questions to ask your oncologist or nuclear medicine specialist

Consider bringing this checklist to your appointment.

Am I eligible? What features of my diagnosis make me a suitable or unsuitable candidate?
Does my cancer express the target? What did my PSMA PET or somatostatin receptor scan show?
Are all important cancer sites target-positive? Is there evidence of lesions that may not respond?
What is the goal? Is treatment intended to delay progression, reduce tumour burden, control symptoms or improve survival?
What are my alternatives? How does this compare with other available treatments for my specific situation?
What is the treatment schedule? How many cycles are expected, and what could cause a delay or cancellation?
What are my personal risks? How do my blood counts, kidney function and previous treatments affect safety?
How will we measure success? Which scans, blood tests, symptoms or biomarkers will be used?
What precautions will I need at home? How should I manage contact with children, pregnant people and other household members?
What will it cost? Is treatment covered, and are the drug, scans, supportive medicines and follow-up included?

11. Frequently asked questions

Is radioligand therapy the same as chemotherapy?

No. Radioligand therapy uses a radioactive medicine attached to a targeting molecule. Chemotherapy uses drugs that act through other anticancer mechanisms. Both can circulate through the body and can produce side effects, but they work differently.

Is radioligand therapy the same as nuclear medicine imaging?

No. Diagnostic nuclear medicine imaging uses a radioactive tracer to show where a biological target is present. Radioligand therapy uses a therapeutic radioactive medicine to deliver a dose of radiation intended to damage cancer cells. A related molecular target may be used for both diagnosis and treatment, an approach sometimes called theranostics.

Does a positive PSMA PET scan mean I can receive Pluvicto?

Not automatically. The scan helps establish whether the cancer expresses PSMA, but eligibility also depends on the disease setting, treatment history, the distribution of lesions, kidney function, blood counts and other clinical factors.

Can Lu-177 PSMA treat every type of prostate cancer?

No. Prostate cancers differ in PSMA expression. Some lesions may have low uptake or lack the target. The decision depends on the patient's scans, pathology and overall clinical circumstances.

Can Lu-177 DOTATATE treat every neuroendocrine tumour?

No. It is used for appropriate somatostatin receptor-positive tumours. The primary site, tumour grade and differentiation, imaging findings and overall clinical situation all matter.

Will I be radioactive after treatment?

Yes, for a period after receiving a radiopharmaceutical, some radiation is emitted from the body and radioactive material is eliminated through bodily fluids. The amount declines over time. Your treating team will provide specific instructions based on the drug and local radiation-safety rules.

Will I need to stay in hospital?

Not always. Some centres provide treatment on an outpatient basis, while others use short hospital stays or observation periods depending on the treatment protocol, radiation measurements, patient needs and local regulations.

Can I continue my other cancer treatments?

Possibly, but the timing and combination must be planned by your oncology team. Other treatments can affect blood counts, kidney function, treatment toxicity or the effectiveness of the overall plan.

Is radioligand therapy available for cancers other than prostate cancer and neuroendocrine tumours?

Other radiopharmaceutical treatments exist, and many additional radioligands are under investigation. However, an investigational treatment is not necessarily approved or proven effective for routine clinical use. Availability and approved indications vary by country.

Can radioligand therapy cure metastatic cancer?

It can produce substantial responses and meaningful disease control in some patients, but a cure should not be assumed. The likelihood of long-term control depends on the cancer type, extent of disease, tumour biology and response to treatment.

12. The bottom line

Radioligand therapy represents an important advance in precision cancer treatment. It uses a molecular targeting system to deliver radiation to cancer cells throughout the body, potentially treating multiple sites of disease with one systemic approach.

For appropriately selected patients, Lu-177 PSMA offers an established option for certain forms of prostate cancer, while Lu-177 DOTATATE is an established treatment for selected somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumours.

Yet the molecular target, not simply the cancer diagnosis, is central to treatment selection. Imaging, laboratory tests, treatment history and overall health all influence whether the approach is likely to help.

The most useful next step for a patient is to ask an oncology or nuclear medicine specialist whether the cancer has the appropriate target, what benefit is realistic in that specific clinical setting, and how treatment risks compare with the alternatives.

Key message: Radioligand therapy is targeted radiation delivered through the bloodstream. It is a valuable option for some patients, not a universal treatment for all cancers.

Sources and further reading

US Food and Drug Administration (FDA). FDA approval of Pluvicto with androgen receptor pathway inhibitor therapy for metastatic hormone-sensitive prostate cancer, July 31, 2026.
US Food and Drug Administration (FDA). FDA expands Pluvicto's metastatic castration-resistant prostate cancer indication, March 28, 2025.
DailyMed / US prescribing information. Pluvicto prescribing information.
DailyMed / US prescribing information. Lutathera prescribing information.
Society of Nuclear Medicine and Molecular Imaging (SNMMI). Radiopharmaceutical therapy and prostate cancer: patient fact sheet.
Society of Nuclear Medicine and Molecular Imaging (SNMMI). Molecular imaging and neuroendocrine tumours: patient fact sheet.
Strosberg J, et al. Phase 3 trial of 177Lu-Dotatate for midgut neuroendocrine tumors. New England Journal of Medicine. 2017;376:125–135. doi:10.1056/NEJMoa1607427.

Medical disclaimer: This article is for general education and is not a diagnosis or individual treatment recommendation. Drug approvals, eligibility rules, treatment protocols and availability may vary by country and may change. Always consult the treating oncology and nuclear medicine team for advice based on your diagnosis, scans, laboratory results and personal circumstances.