PRRT, peptide receptor radionuclide therapy, treats neuroendocrine tumors that have spread by delivering lutetium-177 radiation through the somatostatin receptors on tumor cells, using Lu-177 DOTATATE (Lutathera). Four infusions are given eight weeks apart after a Ga-68 DOTATATE PET scan confirms the receptors. Our nuclear medicine team plans each cycle around your somatostatin injections and follows you once you are back home.
About This Department
Nuclear Medicine
Most neuroendocrine tumors carry receptors for the hormone somatostatin. PRRT uses those receptors to deliver radiation from inside.
PRRT, peptide receptor radionuclide therapy, treats neuroendocrine tumors that have spread or cannot be removed by linking a somatostatin-like peptide to the radioactive metal lutetium-177, in the drug Lu-177 DOTATATE, sold as Lutathera. The peptide finds the somatostatin receptors on tumor cells and the lutetium irradiates them over the following days. A course has four infusions, eight weeks apart. In the NETTER-1 trial of midgut neuroendocrine tumors growing on standard treatment, 65.2 percent of patients on PRRT were alive without progression at 20 months, against 10.8 percent on high-dose octreotide (Strosberg and colleagues, New England Journal of Medicine, 2017). As a first treatment for grade 2 and 3 tumors, it extended median progression-free survival from 8.5 to 22.8 months (Singh and colleagues, Lancet, 2024). A Ga-68 DOTATATE PET/CT scan first confirms the receptors are there. This page explains how PRRT works, who qualifies, the scan that selects patients, trial results, a treatment day, side effects, precautions at home, follow-up, and how patients from abroad arrange PRRT at Biruni Hospital in Istanbul.
65.2
Percent of patients alive without progression at 20 months on PRRT in midgut tumors, against 10.8 percent
22.8
Months median progression-free survival with first-line PRRT in grade 2 and 3 tumors, against 8.5 months
4
Infusions in a standard course, given eight weeks apart
Free
Review of your DOTATATE PET scan and pathology by our nuclear medicine team
Neuroendocrine tumors grow from hormone-producing cells scattered through the gut, pancreas and lungs. Most are slow-growing, and many carry large numbers of somatostatin receptors on their surface. PRRT exploits this. A peptide that mimics somatostatin carries lutetium-177 to the receptors, and its beta radiation, reaching only a couple of millimeters, damages the tumor cells from inside.
1
The drug
Lu-177 DOTATATE combines the peptide octreotate, a chelator called DOTA that holds the metal, and lutetium-177. It is approved in Europe and the United States for gastroenteropancreatic neuroendocrine tumors.
Tumors treated with PRRT
Tumor
Origin
Evidence
Midgut neuroendocrine tumor
Small bowel, appendix, right colon
Randomized trial, NETTER-1
Pancreatic neuroendocrine tumor
Pancreas
Large series, NETTER-2 included
Grade 2 and 3 gastroenteropancreatic tumors
Gut and pancreas
Randomized first-line trial, NETTER-2
Lung carcinoid, paraganglioma, pheochromocytoma
Lungs, nerve tissue
Case series, selected patients
Theranostics
The same receptor seen on the DOTATATE PET scan becomes the target of treatment. What lights up on the scan is what the therapy will reach.
Who qualifies
1
The usual candidate
A patient with a well-differentiated neuroendocrine tumor that has spread or cannot be removed, that is growing or causing symptoms, and that shows strong receptor uptake on DOTATATE PET.
Requirements for PRRT
Requirement
Why
How checked
Well-differentiated tumor, grade 1 to 3
Carries receptors and responds
Pathology with Ki-67
Strong somatostatin receptor uptake
The drug needs the target
Ga-68 DOTATATE PET/CT
Adequate kidney function
The drug leaves through the kidneys
Blood tests, kidney scan if needed
Adequate blood counts and liver function
Marrow and liver tolerance
Blood tests
Poorly differentiated neuroendocrine carcinoma, which behaves more like other aggressive cancers, is treated with chemotherapy rather than PRRT.
The neuroendocrine tumor board reviews each case, weighing PRRT against surgery, liver-directed treatment, somatostatin analog injections, targeted drugs such as everolimus and sunitinib, and chemotherapy.
The scan that selects patients
Ga-68 DOTATATE PET/CT shows where somatostatin receptors are and how many. Uptake stronger than the normal liver predicts benefit from PRRT.
Krenning score of receptor uptake
Score
Uptake compared with normal organs
Suitability
1
Very low
Not suitable
2
Equal to liver
Borderline
3
Greater than liver
Suitable
4
Greater than spleen or kidneys
Most suitable
Every significant tumor should show strong uptake. A large deposit without uptake would escape treatment, and the plan changes.
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FDG PET in higher-grade tumors
For grade 2 and 3 tumors, an FDG PET scan may be added. Deposits that are bright on FDG and dark on DOTATATE are more aggressive and need other treatment.
Why the receptor matters
No receptor, no effect.
PRRT works only as well as the uptake it achieves, so the selection scan carries great weight. A tumor whose every deposit glows brighter than the liver on DOTATATE PET receives a high radiation dose with little spillover to healthy tissue, while one with patchy or weak uptake receives too little to matter and exposes the patient to side effects without much chance of benefit. That single image, read carefully by experienced physicians, decides more about the outcome than any other factor we can measure before treatment.
Grade matters too. Faster-growing tumors lose receptors over time.
Results in midgut tumors
Treatment with Lu-Dotatate resulted in markedly longer progression-free survival and a significantly higher response rate than high-dose octreotide LAR among patients with advanced midgut neuroendocrine tumors (Strosberg and colleagues, 2017).
The final survival analysis showed median overall survival of 48.0 months with PRRT against 36.3 months with octreotide. The 11.7-month difference did not reach statistical significance, partly because many patients in the control group later received PRRT, and the investigators considered it clinically relevant (Strosberg and colleagues, Lancet Oncology, 2021).
NETTER-1, 229 patients with progressive midgut tumors
Measure
PRRT with octreotide
High-dose octreotide
Alive without progression at 20 months
65.2 percent
10.8 percent
Tumor shrinkage
18 percent
3 percent
Median overall survival, final analysis
48.0 months
36.3 months
PRRT as a first treatment
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Grade 2 and 3 tumors
Tumors with a higher Ki-67, meaning faster cell division, carry a worse outlook and had no standard first-line treatment. NETTER-2 tested PRRT at diagnosis in this group.
First-line Lu-Dotatate plus octreotide LAR significantly extended median progression-free survival by 14 months in patients with grade 2 or 3 advanced gastroenteropancreatic neuroendocrine tumors (Singh and colleagues, 2024).
NETTER-2, 226 newly diagnosed patients
Measure
PRRT with octreotide
High-dose octreotide
Median progression-free survival
22.8 months
8.5 months
Treatment-related deaths
None
None
PRRT is now considered a first-line option for these patients when their tumors show strong receptor uptake.
2
Before surgery
In selected patients, PRRT shrinks tumors enough to make an operation possible, an approach still under study.
A treatment day
1
Kidney protection
An infusion of amino acids, lysine and arginine, starts 30 minutes before the drug and runs for about four hours. It blocks the kidneys from holding on to the radioactive peptide.
Anti-sickness medicine is given first, since the amino acids cause nausea in many patients. The Lu-177 DOTATATE itself runs in over about 30 minutes. Patients stay in a shielded room until the radiation level falls below the release limit, a few hours to overnight depending on national rules.
A scan the day after the infusion shows where the drug has gone and confirms it reached the tumors.
Schedule
A standard PRRT course
Step
Timing
Note
Stop long-acting somatostatin analog
4 weeks before each cycle
Short-acting injections until 24 hours before
Infusion day
Day 1 of each cycle
Amino acids and Lu-177 DOTATATE
Post-treatment scan
Day 2
Discharge with precautions
Blood tests
Every 2 to 4 weeks
Counts, kidney and liver
Next cycle
8 weeks later
Four cycles in total
Long-acting octreotide or lanreotide injections resume after each cycle and continue after the course.
Somatostatin analog injections
Most patients already receive octreotide or lanreotide injections, which control hormone symptoms and slow tumor growth. These drugs occupy the same receptors PRRT needs.
Do I have to stop my octreotide or lanreotide injections?
Long-acting injections are paused for about four weeks before each PRRT cycle, so that the receptors are free for the radioactive drug. Patients with flushing or diarrhea from carcinoid syndrome can use short-acting octreotide injections until 24 hours before treatment. The long-acting injection is given again within a day or so after each cycle.
The endocrinologist or oncologist who gives your injections at home coordinates timing with us, and we send a written schedule for each cycle so that nothing depends on memory.
Living with a neuroendocrine tumor
Many patients live with the disease for years. Some for decades.
Neuroendocrine tumors grow slowly in the majority, and even with spread to the liver, patients may work and live full lives for a long time. The aim of treatment is control, of the tumor and of symptoms such as flushing and diarrhea, for as long as possible, choosing each step so that later options remain open. PRRT fits into that plan alongside injections, surgery, liver-directed treatment and targeted drugs.
Side effects
Nausea and vomiting on the day of treatment, mostly from the amino acid infusion.
Tiredness and reduced appetite for a few days.
Temporary hair thinning in some patients, without full hair loss.
Side effects and what helps
Side effect
How often
What helps
Nausea, vomiting
Common on treatment day
Anti-sickness medicine before the infusion
Low blood counts
Serious in a small minority
Blood tests, delay or dose reduction
Kidney changes
Rare with amino acid protection
Monitoring of kidney function
Hormone flare
Uncommon
Short-acting octreotide, extra fluids
In the long-term follow-up of NETTER-1, 2 percent of patients treated with PRRT developed myelodysplastic syndrome, a bone marrow disorder, and blood counts are therefore followed for years.
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Carcinoid crisis
Rarely, a burst of hormone release causes flushing, low blood pressure and wheezing during or soon after treatment. It is treated at once with octreotide and fluids, and patients at high risk receive extra octreotide beforehand.
Precautions at home
Radioactivity from lutetium-177 halves every 6.7 days, and most of the drug leaves the body in urine within two days. Simple steps keep family members safe.
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The first week
Keep a distance from children and pregnant women, sleep in a separate bed, and flush the toilet twice. Drink plenty and empty the bladder often.
Typical precautions after each cycle
Precaution
Usual duration
Note
Distance from children and pregnant women
About one week
Brief contact is fine
Separate bed
About one week
Varies with dose and national rules
Contraception
Several months after the last cycle
For men and women
Carry the treatment card while traveling, since some airport detectors pick up the radioactivity.
Follow-up and retreatment
Follow-up after PRRT
Test
Timing
Purpose
Blood tests
Every 2 to 4 weeks during treatment, then every 3 months
Counts, kidney and liver function
CT or MRI
About 3 months after the last cycle, then regularly
Tumor size
DOTATATE PET/CT
As needed
Receptor status before any retreatment
Tumors often stop growing rather than shrink dramatically, and stable disease is a good result in neuroendocrine tumors.
1
Retreatment
When a tumor that responded well grows again after a long interval, a further two cycles of PRRT can be considered, if blood counts and kidney function allow and the receptors are still present.
The tumor board reviews each scan and advises on the next step.
For patients from abroad
Before you travel
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Length of stay and fitness to fly
Each cycle needs three to five days in Istanbul, for blood tests, the infusion, the post-treatment scan and discharge. Patients are fit to fly after discharge, carrying the radiation card. Four cycles eight weeks apart mean four short trips over about seven months.
Send your pathology report with Ki-67, a recent DOTATATE PET/CT or the images from it, blood tests and a summary of treatment so far. If no PET has been done, we arrange it on arrival. Between cycles, blood tests are done at home and sent to us.
Your coordinator
One coordinator from the international patients office handles arrangements from the first message through discharge and answers the same WhatsApp number once you are back home. The office works in English, Arabic, French, Russian, Serbian, Romanian and Spanish and books interpreters for other languages, and it arranges the visa invitation letter, airport transfers, daily transport and accommodation near the hospital. Halal, vegetarian and diabetic meals, a prayer room on site, and a female physician on request wherever the rota allows.
Blood tests on treatment days, nuclear medicine review
Somatostatin analog injections
PRRT is priced per cycle, and a standard course has four cycles.
Compare quotes for the same drug and number of cycles, and ask whether the PET scan and post-treatment imaging are included.
References
Strosberg J, El-Haddad G, Wolin E, et al. Phase 3 trial of 177Lu-Dotatate for midgut neuroendocrine tumors. N Engl J Med. 2017;376(2):125-135.
Strosberg JR, Caplin ME, Kunz PL, et al. 177Lu-Dotatate plus long-acting octreotide versus high-dose long-acting octreotide in patients with midgut neuroendocrine tumours (NETTER-1). Final overall survival and long-term safety results from an open-label, randomised, controlled, phase 3 trial. Lancet Oncol. 2021;22(12):1752-1763.
Singh S, Halperin D, Myrehaug S, et al. [177Lu]Lu-DOTA-TATE plus long-acting octreotide versus high-dose long-acting octreotide for the treatment of newly diagnosed, advanced grade 2-3, well-differentiated, gastroenteropancreatic neuroendocrine tumours (NETTER-2). An open-label, randomised, phase 3 study. Lancet. 2024;403(10446):2807-2817.
Editor's note
Written by the Biruni Hospital medical editorial team. Reviewed by Specialist Dr. Sedat OFLUOĞLU, Nuclear Medicine.
