DOTAMTATE
Octreotate with a lead-holding DOTAM chelator, built to deliver alpha radiation to neuroendocrine tumours
DOTAMTATE joins octreotate, the somatostatin analogue that finds receptor 2 on neuroendocrine tumours, to DOTAM, a chelator chosen to hold lead. Loaded with lead-212, whose decay chain releases alpha particles, it is an alpha-emitter version of the approved lutetium-177 DOTATATE treatment. A first-in-human trial in 20 patients reported its early results in 2022, and a phase 2 trial is under way. It is not approved anywhere.
Used in human trials: 2.50 MBq per kg (67.6 µCi per kg), Per cycle, 8 weeks apart, Intravenous (Lead-212 DOTAMTATE, SSTR-positive neuroendocrine tumours: recommend...) Details ↓
Recommended Dosing
Used in human trials
No manufacturer dose exists for this use: these are amounts given in published trials, not recommendations.
What is it?
Peptide receptor radionuclide therapy treats neuroendocrine tumours by attaching a radioactive atom to a somatostatin analogue, so the drug travels to cells that carry somatostatin receptor 2 and irradiates them from close range. The approved version, lutetium-177 DOTATATE, uses a beta emitter: its electrons travel comparatively far through tissue. Alpha particles have a much shorter range and deposit far more energy along it (the 2025 review cited below calls this high linear energy transfer), so an alpha emitter could in principle kill tumour cells that resist beta radiation while sparing more of the tissue around them. DOTAMTATE is one attempt to do that. The peptide is the same octreotate used in DOTATATE; the chelator is DOTAM, which holds lead, and the radioactive atom is lead-212. Lead-212 is the parent of an alpha emitter: its decay products release alpha particles where the drug has collected.
The 2019 preclinical paper set out how the drug behaves in mice with neuroendocrine tumours. More than a fifth of the injected activity per gram of tumour was still there 24 hours after injection. Giving the amino acids lysine and arginine lowered how much collected in the kidneys, the organ most at risk with these drugs, and adding ascorbic acid during labelling cut oxidation of the product. A single dose extended average survival 2.4-fold, three cycles two weeks apart did better, and three cycles combined with the chemotherapy drug 5-fluorouracil left 79% of the mice free of tumour at the end of the 31-week study. A 2025 study then compared lead-212 attached to four different somatostatin-receptor compounds in the same tumour model and found that DOTAMTATE gave the best ratio of tumour exposure to kidney exposure.
The first human trial enrolled 20 people with metastatic or inoperable neuroendocrine tumours whose scans showed somatostatin receptors and who had never had radionuclide therapy. Doses were raised in steps of 30% until a response or a dose-limiting side effect appeared, first as single doses and then as repeated cycles. The regimen carried forward to phase 2 was 2.50 MBq per kilogram of body weight, given into a vein four times at eight-week intervals, and ten people received that level. The commonest side effects were nausea, tiredness and hair loss; none of the serious adverse events was attributed to the drug, and no one needed a delay or a lower dose. Eight of the first ten treated at the recommended level had an objective response on imaging. The authors called these results preliminary, and a group of ten is far too small to compare with lutetium-177 DOTATATE.
A phase 2 trial in patients with and without earlier radionuclide therapy (NCT05153772) is active but no longer recruiting. A 2025 review of alpha-emitter therapy reports interim phase 2 figures for lead-212 DOTAMTATE: an objective response rate of 56.8%, disease control in all evaluable patients, and difficulty swallowing in about a third. Those numbers come from the review's summary of meeting reports; no full phase 2 paper was found on PubMed (searched October 29, 2026). DOTAMTATE is prepared in radiopharmacies and given in nuclear-medicine departments within trials. It has no FDA or EMA approval and is not a product anyone can buy or use outside a trial.
At a Glance
Every value in this table is printed from the Grey Peptides dataset, the same record the compound explorer and comparison tool read, so the three can never disagree.
Mechanism of Action
DOTAMTATE carries lead-212 to cells with somatostatin receptor 2. The octreotate part finds the receptor; the DOTAM cage holds the lead, whose decay products release alpha particles inside and next to the tumour.
SSTR2 targeting
The octreotate peptide binds somatostatin receptor 2, which many neuroendocrine tumours carry; tumour uptake stayed above 20% of the injected activity per gram at 24 hours in mice (2019 study).
A chelator suited to lead
In a 2025 comparison, DOTAM took up lead-212 faster and more completely than a lead-specific chelator, and DOTAMTATE gave the best tumour-to-kidney exposure ratio of the compounds tested.
Alpha particles at short range
Lead-212 is the parent of an alpha emitter (2019 study); alpha particles' short range and high energy per track are the reason for building the drug (2025 review).
Published Research
These are the studies of DOTAMTATE read from their PubMed abstracts on October 29, 2026: one trial in patients, a review that reports interim phase 2 figures, two studies in mice and a laboratory test of the drug product. Two records whose titles do not name DOTAMTATE are carded because their abstracts name it as the agent studied; two more that use it only as a test material are listed in References.
First-in-human dose escalation, 20 patients
Twenty people with SSTR-positive neuroendocrine tumours and no earlier radionuclide therapy received rising single and then repeated doses. The recommended phase 2 regimen was four cycles of 2.50 MBq/kg eight weeks apart, given to ten people. Nausea, fatigue and hair loss were the commonest effects; no serious adverse event was attributed to the drug. Eight of the first ten at that level (80%) had an objective radiological response.
Alpha-emitter receptor therapy: review of 150 patients
A review of seven alpha-emitter studies in neuroendocrine tumours reports interim phase 2 results for lead-212 DOTAMTATE: objective response 56.8% and disease control 100%, with difficulty swallowing in 34% of patients. Across the alpha-emitter studies, serious blood and kidney toxicity was uncommon.
Targeting, safety and survival in mice
Tumour uptake exceeded 20% of the injected activity per gram for 24 hours. Lysine and arginine lowered kidney uptake. Single 20 µCi doses were survived by all mice, and 45 µCi split into three doses was not toxic. One 10 µCi dose extended mean survival 2.4-fold; three cycles with 5-fluorouracil left 79% of animals tumour-free at 31 weeks.
Compared with three other lead-212 compounds
Lead-212 was attached to DOTAMTATE, DOTATATE, a somatostatin-receptor antagonist and an octreotide conjugate with a lead-specific chelator, and the four were compared in animals with AR42J tumours, which carry SSTR2. DOTAM chelated lead faster and more efficiently than the lead-specific chelator, and DOTAMTATE had the highest tumour-to-kidney exposure ratio.
The drug product sterilises itself
Vials of lead-212 DOTAMTATE drug product were inoculated with six microorganisms. After 6 hours each showed at least a million-fold fall in colonies at an absorbed dose of no more than 1.01 kGy, and two vials incubated for 14 days grew nothing. The authors work for the company developing the drug.
Dosing Data
DOTAMTATE has no approved label. Like other radiopharmaceuticals it is dosed by radioactivity per kilogram of body weight, not by weight of peptide. The row below is the regimen chosen in the published first-in-human trial, given into a vein in a nuclear-medicine department.
Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
Side Effects & Contraindications
Reported Side Effects
From the first-in-human trial and the 2025 review.
Contraindications & Cautions
No approved label exists, so there are no official contraindications. Points from the studies:
Legal Status
DOTAMTATE is investigational in every jurisdiction checked.
Frequently Asked Questions
?What is DOTAMTATE?
The somatostatin analogue octreotate attached to DOTAM, a chelator that holds lead. Loaded with lead-212, it carries alpha radiation to tumour cells that have somatostatin receptor 2.
?How does it differ from lutetium-177 DOTATATE?
The peptide is the same octreotate. The chelator and the metal differ: lutetium-177 gives off beta particles, while lead-212's decay products give off alpha particles, which have a shorter range and deposit more energy along it.
?Has it been given to people?
Yes. Twenty people with neuroendocrine tumours took part in the first trial, ten of them at the regimen chosen for phase 2, and a phase 2 trial has since finished recruiting.
?Is DOTAMTATE approved?
No. It is investigational in the US and the EU and is given only within clinical trials.
References
- [other] PubChem CID 135228365 (synonyms DOTAMTATE, oxoreotide atexetan): formula C65H93N17O16S2, molecular weight 1432.7. Read October 28, 2026. https://pubchem.ncbi.nlm.nih.gov/compound/135228365
- [clinical-trial] Delpassand ES, et al. "Targeted α-Emitter Therapy with (212)Pb-DOTAMTATE for the Treatment of Metastatic SSTR-Expressing Neuroendocrine Tumors: First-in-Humans Dose-Escalation Clinical Trial." J Nucl Med, 2022;63(9):1326-1333. PMID: 34992153.
- [pubmed] Leupe H, et al. "Clinical Experience with Targeted Alpha-Emitter Peptide Receptor Radionuclide Therapy (α-PRRT) for Somatostatin Receptor-Positive Neuroendocrine Tumors." Pharmaceuticals (Basel), 2025;18(11). PMID: 41304857.
- [pubmed] Stallons TAR, et al. "Preclinical Investigation of (212)Pb-DOTAMTATE for Peptide Receptor Radionuclide Therapy in a Neuroendocrine Tumor Model." Mol Cancer Ther, 2019;18(5):1012-1021. PMID: 30926632.
- [pubmed] Saidi A, et al. "Side-by-Side Comparison of the In Vivo Performance of [(212)Pb]Pb-DOTAMTATE and Other SSTR2-Targeting Compounds." J Nucl Med, 2025;66(3):391-397. PMID: 39884771.
- [pubmed] Schatzmann AT, et al. "Microbial Cytotoxic Effect of (212)Pb in Radiopharmaceuticals." Cancer Biother Radiopharm, 2025;40(4):263-269. PMID: 40019794.
- [pubmed] Zaid NRR, et al. "A Physiologically Based Pharmacokinetic Model for In Vivo Alpha Particle Generators Targeting Neuroendocrine Tumors in Mice." Pharmaceutics, 2021;13(12). PMID: 34959413.
- [pubmed] Bobin C, et al. "Activity standardization and determination of nuclear decay data of (212)Pb at LNE-LNHB and first measurements in the SIR at BIPM." Appl Radiat Isot, 2025;226:112124. PMID: 40876307.
- [registry] ClinicalTrials.gov API v2, read October 28, 2026: NCT05153772 (phase 2, targeted alpha-emitter therapy of PRRT-naive and previously treated neuroendocrine tumours, active, not recruiting).
- [clinicaltrials] ClinicalTrials.gov NCT03466216: "Phase 1 Study of AlphaMedix™ in Adult Subjects With SSTR (+) NET". Phase 1, terminated, February 2018 start, 33 participants. Registry record read October 29, 2026.
Sources & Citations
Studies were read from their PubMed records on October 29, 2026. Regulatory status comes from Drugs@FDA and the EMA medicines list (searched October 28, 2026) and trial listings from ClinicalTrials.gov (read October 29, 2026). Formula and weight are PubChem's. Grey Peptides sells nothing and links to no vendor.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Consult a licensed healthcare provider before making health decisions.