RYZ101 Just Passed Phase 3. How Does a Peptide Deliver Cancer Treatment?

What exactly did Bristol Myers Squibb announce?

Bristol Myers Squibb put the announcement out at 6:55 AM Eastern on October 12, 2026. It says the trial "met the primary endpoint with a statistically significant and clinically meaningful improvement in progression-free survival by blinded independent central review."³

Two pieces of that sentence need unpacking. Progression-free survival means the time a patient lives without their cancer growing or spreading on a scan. Blinded independent central review means the scans were read by radiologists outside the trial, who did not know which treatment each patient had received. That closes off one route by which wishful reading creeps into a result.

The release also gives "safety results consistent with the known RYZ101 safety profile." It says enrolled patients "will be followed for overall survival," and that "detailed results are expected to be presented at a future medical meeting."³

That last sentence matters most. What has been released is a direction, not a size.

How much of a difference did it make?

Nobody outside the company knows, because the figures have not been released.

There is no hazard ratio, no median progression-free survival for either arm, no p-value and no event count. The independent oncology trade press reports the same absence. Both OncLive and CancerNetwork describe the result in the company's own words, and neither adds a figure of its own.⁴⁵

So "statistically significant" tells you the effect is unlikely to be chance, and "clinically meaningful" is the company's own characterisation of the size. Neither is a number. A treatment can clear a statistical threshold by a margin that matters enormously or by one that matters at the edges, and nothing released so far distinguishes those.

For comparison, the approved lutetium-177 version of this idea has published figures. Its label reports a progression-free survival hazard ratio of 0.21 against high-dose long-acting octreotide in the NETTER-1 trial, with a 95% confidence interval of 0.13 to 0.32. Median progression-free survival was not reached in the treatment arm, against 8.5 months in the comparator.² Those figures sit in a table in the label, not in its running text. A result that has been through regulatory review looks like that. RYZ101 has nothing of the kind yet.

What is RYZ101, and why is this called a peptide treatment?

The company describes RYZ101 as "an investigational, targeted radiopharmaceutical therapy comprised of DOTATATE bound to Actinium-225 (225Ac), a highly potent alpha-emitting radioisotope."³ Unpacking that name gives you the whole design.

DOTATATE is two things fused together. TATE is the peptide, a synthetic copy of somatostatin, a hormone your own body makes. DOTA is a chelator, meaning a molecular cage that grips a metal atom and will not let go.

Calling that half a peptide is not loose language, and you do not have to take this page's word for it. The FDA label for the gallium-68 imaging version states it plainly: "Dotatate, also known as DOTA-0-Tyr3-Octreotate, is a cyclic 8 amino acid peptide with a covalently bound chelator (dota)." The same label prints the sequence: H-D-Phe-Cys-Tyr-D-Trp-Lys-Thr-Cys-Thr-OH.⁶ The approved lutetium therapy carries the same chemistry on its own label, where the peptide portion reads as a run of named amino acids: "D-phenylalanyl-L-cysteinyl-L-tyrosyl-D-tryptophanyl-L-lysyl-L-threoninyl-L-cysteinyl-L-threonine-cyclic (2-7) disulfide."² Eight amino acids, with a disulfide bridge tying the second to the seventh to hold the ring shape. That is a peptide by any definition, and its sequence is a matter of public record.

A peer-reviewed review of the field states the principle directly: "the working principle of PRRT is using a therapeutic radionuclide chelated to a SSTR binding peptide."¹ PRRT stands for peptide receptor radionuclide therapy, and the name is accurate about the division of labour. The peptide binds the receptor, and the radionuclide treats.

How does somatostatin receptor targeting work?

Many neuroendocrine tumours carry an unusual number of somatostatin receptors on their surface, and one subtype in particular. That FDA label describes its molecule as binding "to somatostatin receptors with highest affinity for subtype 2 somatostatin receptors (SSTR2)." It then says what happens next: "upon binding to somatostatin receptor expressing cells, including malignant somatostatin receptor-positive tumors, the compound is internalized."²

Internalised is the important word here. The cell does not merely hold the molecule against its surface. It draws the whole thing inside, which puts the radioactive atom in the cell instead of near it. This is also why the trial screened for the receptor instead of enrolling anyone with the diagnosis. Patients had to have receptor-positive disease, confirmed on imaging. A targeting system that works through a receptor is useless on a tumour that does not display one.⁷

The imaging deserves a moment, because it uses the same molecule. Netspot is an FDA-approved PET agent indicated "for localization of somatostatin receptor positive neuroendocrine tumors (NETs) in adult and pediatric patients," and it is gallium-68 attached to dotatate.⁶ Set its chemical name beside the lutetium therapy's and the peptide portion is the same in both. Eight residues in the same order, with the same cyclic 2-to-7 disulfide.²⁶ One peptide, three different metals. Gallium-68 to find the tumour on a scan, lutetium-177 to treat it, actinium-225 in RYZ101. The field calls that a theranostic pair, and it is why a patient can be screened with the same addressing system that will later carry the dose.

What were the options before this?

Thin ones. Filling that gap is what this trial was built to do.

The approved peptide therapy for these tumours is lutetium Lu 177 dotatate, indicated for "adult and pediatric patients 12 years and older with somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut, and hindgut neuroendocrine tumors."² It works, and then for a lot of patients it stops working. What to try next has had no randomised Phase 3 answer at all, which the trial's principal investigator put plainly in the company's own release: "until now there has been no randomized Phase 3 evidence to guide it."³

The comparator arm shows what filling that gap has meant in practice. Patients not receiving RYZ101 got "investigator's choice of standard of care (high-dose or high-frequency long-acting somatostatin analogues, everolimus, or sunitinib)."³ Investigator's choice is the phrase trials use when no single option is established enough to name as the control. Two of those three are not peptides, and none is a second attempt at the mechanism that had already worked and then failed.

So the question ACTION-1 asked was narrow and practical. If the lutetium version bought a patient time and then ran out, does swapping the payload from a beta emitter to an alpha emitter buy more.

Why actinium-225 instead of lutetium-177?

Both isotopes ride the same peptide to the same receptor, and what differs is the kind of radiation they emit.

Lutetium-177 is a beta emitter. Its label states that it "decays to stable hafnium-177 with a half-life of 6.647 days, by emitting beta-minus radiation with a maximum energy of 0.498 MeV."² Actinium-225 is an alpha emitter, described in the peer-reviewed literature as "a pure α-emitter with a half-life of 9.9 days."¹

The practical contrast is reach. The same review gives the typical tissue range of alpha particles as not exceeding 100 micrometres.¹ For lutetium-177 specifically, the European label puts the maximum penetration range in tissue at 2.2 mm with a mean of 0.67 mm.⁸ So the beta particle's maximum reach is roughly twenty times the alpha's, and its mean reach is about seven times. A regulator has put a number on both.

	Lutetium-177	Actinium-225
Radiation	Beta-minus2	Alpha1
Physical half-life	6.647 days2	9.9 days1
Range in tissue	2.2 mm maximum, 0.67 mm mean8	Under 100 µm for alpha particles generally1
Linear energy transfer	0.1 to 1.0 keV/µm1	50 to 230 keV/µm1

Linear energy transfer is how much energy the particle dumps per unit of distance travelled. The alpha figure runs roughly two orders of magnitude higher. That is why the review describes alpha particles as carrying a "higher probability of DNA double strand breaks (DSB) compared to β-particles with low LET." It also notes that cell death can follow "from a single or a few α-particle traversals of the cell nucleus."¹

The two regulators who approved the lutetium version describe the same effect with opposite emphasis. The US label says beta emission "induces cellular damage by formation of free radicals in somatostatin receptor-positive cells and in neighboring cells."² The European summary of product characteristics describes the same molecule as "causing death of the targeted tumour cells with a limited effect on neighbouring normal cells."⁸ One wording leads on the spillover, the other on the limit, and both are accurate about identical physics.

That spillover cuts both ways, which is the real trade-off here. It can help where a tumour holds cells that have lost the receptor and would otherwise receive nothing. It is also radiation going somewhere nobody aimed it. The alpha approach narrows the blast radius to roughly the cell the molecule is sitting in, and accepts that a cell the peptide missed gets no dose at all.

Figures as of October 12, 2026.

What has been peer-reviewed so far?

One peer-reviewed paper has come out of this trial so far, and its subject is dosimetry, meaning the measurement of where the radiation dose actually lands. Published in the Journal of Nuclear Medicine in August 2026, it reports data "obtained from 9 of 17 patients in phase 1b, each completing 4 cycles."⁹ For context on what was given, the Phase 3 portion used a flat dose of 10.2 megabecquerels every eight weeks for four cycles, infused into a vein.⁷

That paper estimated absorbed doses "to kidneys and red bone marrow" of "22.3 and 1.1 Gy, respectively." Tumour doses were reported across a wide range, expressed per unit of administered activity.⁹ Its conclusion is cautious. The data "demonstrated the feasibility of image-based dosimetry of 225Ac," and "the favorable tumor-to-normal tissue absorbed dose ratio of [225Ac]Ac-DOTATATE supports its use."⁹

Feasibility and a favourable dose ratio are real findings, and neither of them is efficacy, which the paper is careful not to claim.

Who was actually in this trial?

Eligibility decides who a result applies to. It is also the part of this story the coverage has least of.

Everyone enrolled had already been treated with the lutetium-177 version and had progressed afterwards. The company's own description is "patients with somatostatin receptor-positive (SSTR+) gastroenteropancreatic neuroendocrine tumors (GEP-NETs) who have progressed following Lutetium-177 (Lu177)-based therapy."³ So this is a second-line question, asked after the existing option has stopped working.

Design documents from the trial itself narrow it further in three ways:

• Enrolment required "grade 1-2, well-differentiated, inoperable, advanced SSTR2+ GEP-NETs," with progression confirmed centrally against the RECIST v1.1 scan criteria used to judge tumour growth.⁷
• Patients were eligible "following 2-4 cycles of therapy with 177Lu-SSA," so a specific amount of prior treatment, not any amount.⁷
• Patients for whom lutetium therapy had never worked were excluded. How large that hurdle was is where two sources disagree, and the disagreement is set out below.

This trial studied people whose cancer responded to lutetium treatment and then progressed. It did not study people whose cancer never responded at all. Whatever its size turns out to be, the result is evidence about that first group and not the other.

On the size of that hurdle, two sources conflict and this page is not going to split the difference. The sponsor's own ACTION-1 poster, presented at ASCO in 2023, gives it as an exclusion: "patients unresponsive to prior 177Lu-SSA (disease control <3 months after 177Lu-SSA) were excluded."⁷ OncLive's eligibility list, published the day of the announcement, makes it a requirement instead. It reports that "patients needed to have achieved disease control for at least 6 months on prior Lu-177 therapy."⁴ Those cannot both describe the same protocol as written. A three-month floor and a six-month floor admit different patient populations, and the six-month version is the stricter of the two.

The poster is the sponsor's description of its own protocol, which makes it the better source on a design question. It is also three years older, which makes it the likelier of the two to have been superseded by an amendment. The trial registry would settle it and could not be read for this page. Until it is settled, the prior-benefit requirement sits somewhere between three and six months of disease control. Any page that gives one figure without mentioning the other has picked a side without saying so.

The trial enrolled 343 patients, a figure reported by OncLive citing the ClinicalTrials.gov record.⁴ The registry entry itself would not render for this page. Treat that number as secondary until the registry or a published paper confirms it.

The name carries one more wrinkle. Bristol Myers Squibb calls it "Phase 3 ACTION-1." Its own publications register it as a "2-part, randomized, controlled, open-label, phase 1b/3 trial." Part one was a small dose-finding study of 6 to 18 patients.⁹⁷ Both descriptions are accurate about different parts of the same study.

Is this the first alpha treatment for cancer?

No, and the company has not claimed it is. The distinction it did claim is narrower, and coverage tends to drop the qualifier.

An alpha-emitting cancer drug has been FDA-approved since 2013. Xofigo, radium Ra 223 dichloride, is indicated for castration-resistant prostate cancer with "symptomatic bone metastases and no known visceral metastatic disease," and its label describes the active moiety as "the alpha particle-emitting isotope radium-223."¹⁰

What radium-223 does not have is a targeting molecule. Its label says the isotope "mimics calcium and forms complexes with the bone mineral hydroxyapatite at areas of increased bone turnover, such as bone metastases."¹⁰ No peptide, no receptor, no address. The chemistry takes it to bone because radium behaves like calcium, which works well for bone metastases and not at all for anything else.

That label is also the plainest published account of why anyone wants alpha particles. It gives "the high linear energy transfer of alpha particles (80 keV/micrometer)" as leading to "a high frequency of double-strand DNA breaks in adjacent cells." It puts the range at "less than 100 micrometers (less than 10 cell diameters) which limits damage to the surrounding normal tissue."¹⁰ Less than ten cell diameters is a regulator's own gloss on the figure this page has been quoting from a review.

So the claim in the release is about targeted alpha therapy. That means an alpha emitter plus a molecule that chooses where it goes. Radium-223 is the first half without the second. RYZ101 is both, and the word "targeted" is doing all the work in that sentence.

Why is RYZ101 still investigational?

Meeting a primary endpoint at an interim analysis is a milestone inside a trial. Nobody involved calls it an approval, the company included.

The announcement says RayzeBio "plans to engage with the FDA to discuss next steps toward a regulatory submission."³ In plain terms, that conversation has not happened yet. The FDA granted RYZ101 orphan drug designation for GEP-NETs in August 2026.³ The status brings development incentives for rare diseases. No part of it is a finding that a drug works. The release's own forward-looking statement also concedes that RYZ101 "may not receive regulatory approval for the indication described in this release."³

The comparator arm says what the current standard of care actually is. Patients not receiving RYZ101 got "investigator's choice of standard of care (high-dose or high-frequency long-acting somatostatin analogues, everolimus, or sunitinib)."³ Two of those three are not peptides at all.

Does this mean peptides can treat cancer?

A peptide delivered a cancer treatment here. Carrying a treatment is a real and useful job. Being the treatment is a different one.

Strip RYZ101 into parts and the peptide is the least exotic component. Its sequence is published on an FDA label. The hormone it copies is somatostatin, and octreotide, the parent drug, has been an approved prescription medicine for decades; we have a compound page on octreotide. What makes RYZ101 a cancer drug sits in the other components. The chelator is engineered to hold one specific metal, and the isotope has a 9.9-day half-life and is produced under nuclear regulation. The route is an intravenous infusion in a nuclear medicine facility, with eight weeks between cycles because of what the radiation does.¹³⁷

So this story carries no read-across to the peptides sold online as research chemicals. Nothing about RYZ101 was ever bottlenecked on the peptide, and the peptide is the only part of it a supplier could make.

The actual bottleneck is the isotope, and a national laboratory has put numbers on it. Oak Ridge National Laboratory said in November 2021 that it "presently produces the majority of the world's Ac-225 by harvesting it from a supply of thorium-229." The yield is "about 1 curie annually," which the laboratory called "not enough even for large-scale clinical trials." Actinium-225, in its words, is "a radioisotope that doesn't occur in nature," and the short supply is a major barrier to targeted alpha therapy. Proton accelerators at Los Alamos and Brookhaven are being brought in to help.¹¹ Those figures are from 2021 and will have moved. The scale is what matters here, because this is a supply chain measured in curies per year across national laboratories.

Nobody is a few steps away from this with a vial and some bacteriostatic water. The published peptide sequence does not change that, and neither would the chelator.

There is a narrower statement available, and it is the more interesting one. Peptides are good at finding things. Attach one to something that does damage, and you have a way of choosing which cells receive the damage. That principle is what PRRT is. It has one approved drug behind it already, and RYZ101 is a test of how far it extends.

What to watch next

Specific events will tell you more than any further commentary on the topline:

• The medical meeting. Bristol Myers Squibb has committed to presenting detailed results at "a future medical meeting," which is where a hazard ratio, the medians and the full safety tables normally appear.³ Until then the size of the effect stays private.
• The overall survival data. Progression-free survival measures scans. Overall survival measures deaths, takes longer to mature, and enrolled patients "will be followed" for it.³ A progression-free survival win does not guarantee a survival win.
• The regulatory submission. Engaging the FDA on next steps is not a filing, and a filing is not an approval. Each is a separate, datable event, and the gaps between them are where most investigational drugs spend their time.

Common questions

What is RYZ101?

Can peptides actually deliver cancer treatments?

Did the Phase 3 trial show how much better RYZ101 is?

Is RYZ101 approved or available?

What is the difference between actinium-225 and lutetium-177?

Does the shorter range make actinium better?

Who was eligible for the ACTION-1 trial?

Why does that exclusion matter?

What comes after Lutathera stops working?

Is this the same thing as octreotide?

What does PRRT mean?

Is RYZ101 the first alpha therapy for cancer?

Is the same peptide used to scan for the tumour before treating it?

Why can nobody buy actinium-225?

Is this related to the peptides sold online?

What are gastroenteropancreatic neuroendocrine tumours?

Has anything from this trial been peer-reviewed?

Why is it called Phase 3 if the registry says phase 1b/3?

Should a patient with neuroendocrine tumours ask about this?

Sources

1. Shi M, Jakobsson V, Greifenstein L, Khong PL, Chen X, Baum RP, Zhang J. Alpha-peptide receptor radionuclide therapy using actinium-225 labeled somatostatin receptor agonists and antagonists. Frontiers in Medicine 2022;9. doi:10.3389/fmed.2022.1034315. Read at source, open access peer-reviewed review. States that actinium-225 is "a pure α-emitter with a half-life of 9.9 days." Gives alpha linear energy transfer as "ranging from 50 to 230 keV/μm" against "low LET (0.1-1.0 keV/μm)" for beta particles, and the typical tissue range of alpha particles as not exceeding 100 μm against "0.05-12 mm" for beta particles. States that alpha particles carry a "higher probability of DNA double strand breaks (DSB) compared to β-particles with low LET" and that cell death can occur "from a single or a few α-particle traversals of the cell nucleus." Defines the field: "the working principle of PRRT is using a therapeutic radionuclide chelated to a SSTR binding peptide." Its Table 1 gives a lutetium-177 half-life of 160.8 hours, which agrees with the 6.647 days in reference 2.
2. LUTATHERA (lutetium Lu 177 dotatate) injection prescribing information, Novartis. Revised 10/2024. Read at source. Section 1: "LUTATHERA is indicated for the treatment of adult and pediatric patients 12 years and older with somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut, and hindgut neuroendocrine tumors." Section 11 gives the chemical name, whose peptide portion reads "D-phenylalanyl-L-cysteinyl-L-tyrosyl-D-tryptophanyl-L-lysyl-L-threoninyl-L-cysteinyl-L-threonine-cyclic (2-7) disulfide." Section 11.1: "Lutetium-177 decays to stable hafnium-177 with a half-life of 6.647 days, by emitting beta-minus radiation with a maximum energy of 0.498 MeV (79%) and photonic radiation (γ) of 0.208 MeV (11%) and 0.113 MeV (6.2%)." Section 12.1: binds "to somatostatin receptors with highest affinity for subtype 2 somatostatin receptors (SSTR2)"; "upon binding to somatostatin receptor expressing cells, including malignant somatostatin receptor-positive tumors, the compound is internalized"; "the beta-minus emission from lutetium-177 induces cellular damage by formation of free radicals in somatostatin receptor-positive cells and in neighboring cells." Section 14 names NETTER-1 (NCT01578239). The progression-free survival hazard ratio of 0.21 (95% CI 0.13-0.32) and the comparator median of 8.5 months appear in Table 9 and not in the running text, which is flagged here because a figure read from a table is easier to misattribute than one read from a sentence.
3. Bristol Myers Squibb, "Bristol Myers Squibb Announces Positive Topline Results from the Interim Analysis of Phase 3 ACTION-1 for RYZ101, RayzeBio's Radiopharmaceutical Therapy, in Patients with GEP-NETs," October 12, 2026, 6:55 AM EDT via Business Wire. Release text read at source via a syndicated copy on WQOW MarketMinute, because the Business Wire original and the Bristol Myers Squibb newsroom copy both returned no body text to this page's tooling. Quotes the study as having "met the primary endpoint with a statistically significant and clinically meaningful improvement in progression-free survival by blinded independent central review," with "safety results consistent with the known RYZ101 safety profile," participants to be "followed for overall survival," and "detailed results are expected to be presented at a future medical meeting." Describes the population as "patients with somatostatin receptor-positive (SSTR+) gastroenteropancreatic neuroendocrine tumors (GEP-NETs) who have progressed following Lutetium-177 (Lu177)-based therapy," and the design as "a randomized Phase 3 clinical trial evaluating RYZ101 (225Ac-DOTATATE) versus investigator's choice of standard of care (high-dose or high-frequency long-acting somatostatin analogues, everolimus, or sunitinib)." Describes the drug as "an investigational, targeted radiopharmaceutical therapy comprised of DOTATATE bound to Actinium-225 (225Ac), a highly potent alpha-emitting radioisotope." States that "the FDA granted RYZ101 Orphan Drug Designation for the treatment of GEP-NETs in August 2026" and that the company "plans to engage with the FDA to discuss next steps toward a regulatory submission." Its forward-looking statement notes that RYZ101 "may not receive regulatory approval for the indication described in this release." Attributed quotes from Amreen Husain, MD, chief medical officer of RayzeBio, and Simron Singh, MD, principal investigator of ACTION-1.
4. RYZ101 Meets Primary PFS End Point in Phase 3 ACTION-1 Trial for Post-Lutetium-177 GEP-NETs, OncLive, October 12, 2026. Read at source. Independent oncology trade coverage. Reports no numerical efficacy results. States "the trial enrolled 343 patients," citing the ClinicalTrials.gov record; that enrolment figure reaches this page through secondary coverage, because the registry entry would not render. Reports the August 2026 orphan drug designation and that the company plans to engage the FDA on next steps. Makes no mechanistic comparison between actinium-225 and lutetium-177.
5. RYZ101 Improves Progression-Free Survival in Previously Treated GEP-NETs, CancerNetwork, October 12, 2026. Read at source. Independent oncology trade coverage, cited here as a second outlet confirming that no figures were released. Gives no hazard ratio, median or event count. Describes the mechanism as "DOTATATE bound to actinium-225 (225Ac), a highly potent alpha-emitting radioisotope that emits a high-energy, short-range alpha particle capable of causing double-stranded DNA damage in cancer cells."
6. NETSPOT (kit for the preparation of gallium Ga 68 dotatate injection) prescribing information, revised 12/2021, hosted by FDA. Read at source. Section 1 indicates it, after radiolabeling with Ga 68, "for use with positron emission tomography (PET) for localization of somatostatin receptor positive neuroendocrine tumors (NETs) in adult and pediatric patients." Section 11 is the clearest regulatory statement available that the targeting moiety is a peptide: "Dotatate, also known as DOTA-0-Tyr3-Octreotate, is a cyclic 8 amino acid peptide with a covalently bound chelator (dota)," with the sequence given as "H-D-Phe-Cys-Tyr-D-Trp-Lys-Thr-Cys-Thr-OH" and the full chemical name matching the peptide portion of the lutetium therapy's name at reference 2. Section 12.1: "Ga 68 dotatate binds to somatostatin receptors, with highest affinity for subtype 2 receptors (sstr2)." The document carries the standard caution that it may not be the latest approved version, so the imaging indication should be re-checked against the current label before anyone relies on it clinically. This label does not itself mention the therapy; the pairing claim on this page rests on comparing its chemical name with the one at reference 2, both read at source.
7. Morris M, Ulaner GA, Halperin D, Strosberg J, Mehr S, Li D, Soares H, Anthony L, Kotiah S, Jacene H, Pavel M, Kunz PL, Ferreira D, Li J, Ma K, Rearden J, Moran S, Hope T, Singh S. ACTION-1 phase Ib/3 trial of RYZ101 in somatostatin receptor subtype 2-expressing GEP-NET progressing after 177Lu somatostatin analogue therapy, poster, 2023 ASCO Annual Meeting, June 2-6, 2023, Chicago. Read at source, hosted by the trial sponsor, so a conference poster and not a peer-reviewed paper. Describes ACTION-1 as "a 2-part, global, randomized, controlled, open-label, Phase 1b/3 trial comparing treatment with RYZ101 to standard-of-care therapy," with part one an uncontrolled dose de-escalation of N=6-18 using a Bayesian optimal interval design. Eligibility: "adults with grade 1-2, well-differentiated, inoperable, advanced SSTR2+ GEP-NETs" and "progressive GEP-NET based on RECIST v.1.1 (centrally confirmed) following 177Lu-SSA DOTATATE or 177Lu-DOTATOC," eligible "following 2-4 cycles of therapy with 177Lu-SSA." Exclusion: "patients unresponsive to prior 177Lu-SSA (disease control <3 months after 177Lu-SSA) were excluded." Gives the phase 3 regimen as "a flat dose of 10.2 MBq every 8 weeks for 4 cycles." Does not state a randomisation ratio or a total planned enrolment for part two.
8. Lutathera 370 MBq/mL solution for infusion, summary of product characteristics, European Medicines Agency. Read at source. Section 2: "Lutetium-177 has a half-life of 6.647 days," decaying "by β emission to stable hafnium-177," with "the most abundant β- (79.3%) having a maximum energy of 0.498 MeV" and an average beta energy of "approximately 0.13 MeV," plus low gamma at 113 keV (6.2%) and 208 keV (11%). Section 5.1 gives the figure this page needed and the US label does not carry: lutetium-177 is "a β emitting radionuclide with a maximum penetration range in tissue of 2.2 mm" and a "mean penetration range of 0.67 mm." Section 5.1 also describes the mechanism as having "high affinity for subtype 2 somatostatin receptors (SSTR2)," binding "to malignant cells which overexpress SSTR2," and "causing death of the targeted tumour cells with a limited effect on neighbouring normal cells." That last phrase is quoted on this page against the US label's wording at reference 2, because the two regulators emphasise opposite halves of the same effect.
9. Sgouros G, Ulaner GA, He B, Ghaly M, Frey E, Kotiah S, Scott A, Ferreira D, Sneeden E, Morris M. Dosimetry Results from the Phase 1b/3 ACTION-1 Trial of [225Ac]Ac-DOTATATE (RYZ101) in Patients with Somatostatin Receptor-Expressing, Well-Differentiated GEP-NETs. Journal of Nuclear Medicine 2026;67(8):1239-1246. doi:10.2967/jnumed.125.270573. Read at source. The only peer-reviewed publication from this trial, and it reports dosimetry, not efficacy. States that "dosimetry data were obtained from 9 of 17 patients in phase 1b, each completing 4 cycles," that the drug "was administered intravenously every 8 wk for 1-4 cycles," and that "the mean total administered activity per patient was 31.67 ± 6.57 MBq (range, 21.1-42.5 MBq)." Estimated absorbed doses "to kidneys and red bone marrow were 22.3 and 1.1 Gy, respectively," with tumour doses reported per unit of administered activity across a wide range. Concludes that the data "demonstrated the feasibility of image-based dosimetry of 225Ac" and that "the favorable tumor-to-normal tissue absorbed dose ratio of [225Ac]Ac-DOTATATE supports its use." Describes the study as "a 2-part, randomized, controlled, open-label, phase 1b/3 trial."
10. XOFIGO (radium Ra 223 dichloride) injection prescribing information. Label text read at source via a drug-information host rather than from FDA, which is flagged here because this page uses it to narrow a claim about priority. Highlights give "Initial U.S. Approval: 2013." Section 1 indicates it "for the treatment of patients with castration-resistant prostate cancer, symptomatic bone metastases and no known visceral metastatic disease." Section 11: "Radium-223 has a half-life of 11.4 days," and "the six-stage-decay of radium-223 to stable lead-207 occurs via short-lived daughters, is accompanied predominantly by alpha emissions." Section 12.1: "the active moiety of Xofigo is the alpha particle-emitting isotope radium-223 (as radium Ra 223 dichloride), which mimics calcium and forms complexes with the bone mineral hydroxyapatite at areas of increased bone turnover, such as bone metastases"; "the high linear energy transfer of alpha particles (80 keV/micrometer) leads to a high frequency of double-strand DNA breaks in adjacent cells including tumor cells, osteoblasts and osteoclasts"; and "the alpha particle range from radium-223 dichloride is less than 100 micrometers (less than 10 cell diameters) which limits damage to the surrounding normal tissue." The range figure is specific to radium-223 and is deliberately not used in this page's actinium-225 column, because alpha particles from different isotopes do not share a single range.
11. Tri-Lab effort makes strides toward increasing supply of Ac-225, Oak Ridge National Laboratory, November 17, 2021. Read at source. States that ORNL "presently produces the majority of the world's Ac-225 by harvesting it from a supply of thorium-229," that the amount currently milked from it is "about 1 curie annually," and that this "is not enough even for large-scale clinical trials." Describes the limited supply of actinium-225, "a radioisotope that doesn't occur in nature," as "a major barrier to harnessing its promise for targeted alpha therapy cancer treatment." Reports that "thorium-232 targets are irradiated in proton accelerators at Los Alamos and Brookhaven national laboratories," and quotes a Brookhaven scientist saying "we demonstrated that the accelerator route can generate about 60% of the current annual supply of Ac-225 in just 12 days." Figures are as of November 2021 and will have changed.

Citing this page. Peptide Decoding. RYZ101 Just Passed Phase 3. How Does a Peptide Deliver Cancer Treatment? Trial and isotope figures as of October 12, 2026. https://peptidedecoding.com/news/ryz101-phase-3