RYZ101 (actinium-225 dotatate)_Dosage, benefits & legal status
Also known as RYZ-101, 225Ac-DOTATATE, Ac-225 dotatate, actinium Ac 225 dotatate, actinium (225Ac) oxodotreotide
Its phase 3 result, and how actinium differs from Lutathera's lutetium, is covered in the ACTION-1 trial report.
The same tumour-seeking peptide as Lutathera with a far more destructive alpha-emitting payload, still in trials.
Common vial size is what vendors typically sell, not a recommendation. Enter your own vial in the calculator.
What is RYZ101 (actinium-225 dotatate)?
Plain language first. The technical label stays, but it never stands alone.Overview
It aims at the same somatostatin receptor as Lutathera with stronger, shorter-range radiation, for tumours that grew back after lutetium therapy. On 12 October 2026 BMS said the phase 3 ACTION-1 trial beat standard treatment on progression-free survival at a planned interim analysis, without releasing any numbers. It is not approved anywhere.
RYZ101 is DOTA-octreotate, the eight-residue peptide and cage used in Lutathera, loaded with actinium-225 instead of lutetium-177. Actinium-225 and its decay products release four alpha particles that travel only a few cell widths but break both strands of DNA. RayzeBio developed it, and Bristol Myers Squibb bought RayzeBio for about $4.1 billion in a deal agreed in December 2023.
What it's used for
An experimental hospital radiation treatment for gut and pancreatic neuroendocrine tumours that have progressed after lutetium-177 therapy.
How does RYZ101 (actinium-225 dotatate) work?
What it does in the body, and where.RYZ101 keeps Lutathera's homing peptide and swaps the radioactive atom for an alpha emitter.
- 01Same targetThe octreotate peptide binds somatostatin receptor 2, carried by 80 to 90% of gut and pancreatic neuroendocrine tumours, and the cell pulls the drug inside.
- 02Alpha radiationActinium-225 decays through a chain that releases four alpha particles. Each travels only about 47 to 85 micrometres, a few cell widths, but deposits so much energy that it breaks both strands of DNA.
- 03Why after lutetiumLutetium's beta particles travel millimetres and spread their energy more thinly. The bet is that tumours that survived lutetium remain vulnerable to concentrated alpha damage.
A schematic of the compound's mechanism, not a diagnostic image.
What else is it used for?
Each group carries its own evidence level.Approved means regulators have cleared it for that purpose. Investigational means it is in trials. Early research means it is being studied and is not established.
Phase 3 ACTION-1
Investigational- No dataMet its primary endpoint at a planned interim analysis; the size of the benefit has not been released.
- No dataThe comparison was against high-dose somatostatin analogues, everolimus or sunitinib, not placebo and not more lutetium.
Phase 1b
Investigational- human-early17 people whose tumours had grown after lutetium therapy: 1 complete and 4 partial responses, disease control in 14.
- human-earlySevere side effects of any cause in 52.9%; one death from liver failure, judged unrelated.
Academic actinium-225 dotatate
Investigational- Human observation91 people in New Delhi given actinium-225 dotatate with capecitabine: 24-month progression-free survival 67.5% and overall survival 70.8%, in an uncontrolled series.
The 12 October 2026 result came from a planned interim analysis, and the comparator was standard treatment (high-dose somatostatin analogues, everolimus or sunitinib), not placebo or repeat lutetium. No hazard ratio or median has been released. '120 kBq/kg' was the phase 1b starting dose; phase 3 uses a fixed 10.2 MBq. The 343 enrolled covers the whole phase 1b/3 record; the phase 3 size has not been disclosed. It is not the first alpha-emitting cancer drug: radium-223 (Xofigo) was approved in 2013, but it has no targeting peptide. Only orphan designation has been reported, not fast track or breakthrough. It uses DOTATATE, not DOTATOC.
The published record
Papers and trials about RYZ101 (actinium-225 dotatate)
15 papers tagged human · 7 not reviews or lab · 1 clinical trial publications
5 registered trials · none with posted results
Furthest stage reached: Phase 3, under way
Counted from Europe PMC indexing, not read by a person; a human tag can land on reviews, commentary or lab papers; clinical trial publications is the narrower count.
At a glance
Four things to know about RYZ101 (actinium-225 dotatate)
Evidence
Investigational
Category
Sexual and hormonal
Common vial
Varies
Half-life
Not published in people (actinium-225 decays over 9.9 days)
How much, and do you cycle it?
The range, and whether you take breaks.10.2 MBq every 8 weeks, 4 doses (phase 3), every 8 weeks, for 4 doses. One course of 4 doses, 8 weeks apart Trial dose
ACTION-1 gives up to 4 cycles 8 weeks apart; 15 of the 17 phase 1b patients completed all four.
Not published in people (actinium-225 decays over 9.9 days)Trial protocol
Actinium-225 has a physical half-life of 9.92 days. No blood half-life or clearance for RYZ101 has been published; ACTION-1 includes a pharmacokinetic substudy. Lutathera, the same peptide with lutetium, leaves the blood with a half-life of about 71 hours.
Source: US DOE actinium-225 product information; no human pharmacokinetics published for RYZ101
You can compare this against the whole library to see where it sits.
What does it cost?
Typical dose and cost, in plain numbers.RYZ101 (actinium-225 dotatate) is not reconstituted
It is not supplied as a powder measured in milligrams, so there is no water-to-powder math and no draw to calculate here. Doses are written in MBq.
Typical dose: 10.2 MBq every 8 weeks, 4 doses (phase 3)
Phase 3 dose: a fixed 10.2 MBq (275 microcuries) by intravenous infusion every 8 weeks, for 4 doses. The phase 1b started at 120 kBq per kg of body weight (median 8.3 MBq given) and the fixed dose was chosen from it. That is about 700 times less radioactivity than Lutathera's 7.4 GBq, because each actinium decay chain delivers far more energy. Trial-only, in a licensed nuclear medicine unit; the vial calculator does not apply.
How do you store it?
Before mixing, and after.Dry powder in the freezer or fridge. Once mixed, fridge, and use within about a month.
Unmixed lyophilized RYZ101 (actinium-225 dotatate) keeps for a long time cold. Once you add water the clock starts: most reconstituted vials hold up for roughly 28 to 30 days at fridge temperature. Keep it out of light, and do not freeze it after mixing.
What are the side effects and cautions?
Known cautions and warnings for this compound.Solubility, computed: 38% charged residues, 50% hydrophobic. Water usually sufficient.
A first-pass rule from peptide manufacturers' guidance. It does not account for disulfide bridges, salt form or how the powder was dried, and it predicts what should be easy rather than what will happen in your vial.
Who should avoid it
- Kidney function below an eGFR of 60, excluded from the phase 3
- Pregnancy or breastfeeding, given the radiation
- Earlier radioembolisation, or radioligand therapy other than lutetium-177 somatostatin drugs, excluded from the phase 3
- Poorly controlled diabetes (HbA1c of 8% or more), excluded
- Cirrhosis or a liver transplant, excluded
Stop and get help
- Fever, repeated infections, unusual bruising or bleeding
- Passing much less urine, or new swelling of the legs
- Flushing, diarrhoea, wheezing or a racing heart within a day of a dose
Common effects
- In the 17-person phase 1b: anaemia and nausea in 58.8%, tiredness in 52.9%, weight loss in 47.1%
- Falling kidney clearance in 35.3%, severe and treatment-related in 17.6%
- Severe treatment-related side effects in 29.4%, mostly anaemia and low lymphocytes
- No treatment-related serious adverse events and no dose-limiting toxicities in phase 1b
Where this page says nothing is established, that means nobody has studied it, not that a compound is safe.
Is RYZ101 (actinium-225 dotatate) approved?
And where the numbers on this page come from.No. RYZ101 (actinium-225 dotatate) is not approved anywhere and is currently in company-run clinical trials. There is no legal route to obtain it outside a trial.
- Approval statusInvestigational
- RouteInto a vein, in a nuclear medicine unit
- Checked13 October 2026
- DoseFrom published clinical trials. Not approved by a regulator for this dose.
- Vial sizeFrom what vendors typically list; not a recommendation.
- SourcesBristol Myers Squibb, ACTION-1 interim topline results (12 Oct 2026)ClinicalTrials.gov, ACTION-1 (NCT05477576)Halperin DM et al., ACTION-1 phase 1b, ASCO 2024 posterHalperin DM et al., NANETS 2024 abstract C17FDA GSRS substance record, actinium Ac 225 dotatate (UNII SP9ZNW6WAK)US DOE Isotope Program, actinium-225 product informationBallal S et al., Journal of Nuclear Medicine 2023;64:211-218Bristol Myers Squibb, agreement to acquire RayzeBio (8-K, 26 Dec 2023)
What has happened recently
Not approved anywhere. ACTION-1 (NCT05477576), a randomised open-label phase 1b/3 against the investigator's choice of high-dose somatostatin analogues, everolimus or sunitinib, met its primary endpoint of progression-free survival by blinded central review at a planned interim analysis, announced on 12 October 2026. RayzeBio plans to discuss next steps towards a filing with the FDA, and the data will be presented at a medical meeting. The FDA granted orphan drug designation for these tumours in August 2026; no fast track or breakthrough designation has been reported. Its INN is actinium (225Ac) oxodotreotide. Actinium-225 supply is limited worldwide, and RayzeBio built its own radiopharmaceutical plant in Indianapolis.
You can compare this against the whole library, or read how to check a seller.
What else is like RYZ101 (actinium-225 dotatate)?
Others in Sexual and hormonal, side by side.If you're weighing RYZ101 (actinium-225 dotatate), it's worth reading Terlipressin (Terlivaz), Toremifene, and PT-141 (Bremelanotide) in the same class.
The same tumour-seeking peptide as Lutathera with a far more destructive alpha-emitting payload, still in trials.
- Dose
- 10.2 MBq every 8 weeks, 4 doses (phase 3)
- How often
- Every 8 weeks, for 4 doses
A hospital-only vasopressin analog for hepatorenal syndrome, with a boxed warning for fatal respiratory failure.
- Dose
- 0.85 to 1.7 mg every 6 hours (label)
- How often
- Every 6 hours for up to 14 days
A SERM with a boxed warning for a heart rhythm that can kill.
- Dose
- 60 mg per day
- How often
- Daily
An approved shot that boosts sexual desire through the brain.
- Dose
- 1.75 mg per dose
- How often
- As needed, before activity
Guides for this compound
- How to Reconstitute a Peptide
Mix peptide powder with bacteriostatic water, step by step.
- How to Read an Insulin Syringe
Read the units, convert to millilitres, and draw the exact dose.
- mcg vs mg: The Peptide Dosing Mistake to Avoid
Your vial says mg and your protocol says mcg. Here is the conversion and how to check it.
- How to Read a Peptide COA
What the purity number does and does not tell you, and how to spot an edited report.
- How to Vet a Peptide Vendor
Independent COAs, HPLC purity, and the red flags that mean walk away.
Sources
- Bristol Myers Squibb, ACTION-1 interim topline results (12 Oct 2026)(2026)Primary endpoint of progression-free survival by blinded central review met at a planned interim analysis against investigator's-choice standard care; no figures released; FDA orphan designation in August 2026.
- ClinicalTrials.gov, ACTION-1 (NCT05477576)(2026)Phase 1b/3, 343 enrolled in total; progression after 2 to 4 cycles of lutetium-177 therapy with at least 6 months of control; eGFR of 60 or more; primary analysis planned after 143 events.
- Halperin DM et al., ACTION-1 phase 1b, ASCO 2024 poster(2024)17 patients at 120 kBq/kg: confirmed response 29.4% (1 complete, 4 partial), disease control 82.4%; severe treatment-related events 29.4%; fixed 10.2 MBq chosen for phase 3.
- Halperin DM et al., NANETS 2024 abstract C17(2024)'A fixed dose of 10.2 MBq was declared the recommended phase 3 dose'; median administered activity 8.3 MBq.
- FDA GSRS substance record, actinium Ac 225 dotatate (UNII SP9ZNW6WAK)(2025)INN actinium (225Ac) oxodotreotide; CAS 2864473-30-1; MW 1657.63. Same DOTA-octreotate structure as Lutathera.
- US DOE Isotope Program, actinium-225 product information(2025)Half-life 9.920 days; available weekly but supply is limited.
- Ballal S et al., Journal of Nuclear Medicine 2023;64:211-218(2023)Academic actinium-225 dotatate (not RYZ101) with capecitabine in 91 people in India: partial response in 48% of 79 assessable, 24-month progression-free survival 67.5%.
- Bristol Myers Squibb, agreement to acquire RayzeBio (8-K, 26 Dec 2023)(2023)$62.50 per share in cash, about $4.1 billion.
Beyond these, 20 records are indexed. Browse the records