Satoreotide

JR11, DOTA-JR11 (OPS201, IPN01072; Lu-177 satoreotide tetraxetan), NODAGA-JR11 (OPS202, IPN01070; Ga-68 satoreotide trizoxetan); also LM3 and other "SSTR antagonist" radioligands as a class

Oncology & imaging
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1What it is

Satoreotide is a somatostatin analogue designed to do the opposite of octreotide (#124) at the receptor: it binds SSTR2 but does not switch it on. For a long time nuclear-medicine researchers assumed an was needed, because agonists trigger internalisation that traps the radioactive metal inside the cell. Work in Basel and Boston in the mid-2000s showed that antagonists, despite not internalising, bound to several times more receptor sites and stayed on the tumour longer, giving higher tumour doses in animal and then human studies. JR11 emerged as the lead antagonist and was renamed satoreotide when it entered formal development. The Ga-68 imaging version (OPS202) and the Lu-177 therapy version (OPS201) were taken through Phase I/II by a pharmaceutical sponsor; the project's current status after that programme is unclear †.


2How it's thought to work

More binding sites. bind only the "active" receptor conformation; antagonists bind both active and inactive states, so in tumour tissue the number of accessible binding sites can be 5–10 times higher (Ginj 2006).
Slower wash-out. despite no internalisation, the antagonist-receptor complex dissociates slowly, so tumour retention of Lu-177 is comparable to or longer than with DOTATATE.
Consequence for therapy. higher tumour absorbed dose per GBq injected — but also higher bone-marrow dose, which turned out to be the clinical limitation.
Consequence for imaging. higher tumour-to-background contrast and detection of more lesions than Ga-68 DOTATOC in a head-to-head study.
A somatostatin receptor antagonist used as a radioligand. It is not internalised, yet labels more receptor sites per cell than an agonist does, which is the counter-intuitive finding behind it.Schematic — not to scale

3What the research shows

Lu-177 satoreotide tetraxetan in progressive NETs

An open-label multicentre Phase I/II (n=40) across eight centres reported an objective response rate of 21% and disease control of 95% in the per-protocol population, with investigator-assessed median PFS of 28 months. Grade ≥3 treatment-related adverse events occurred in 43%, almost all haematological; two patients (5%) developed therapy-related myeloid neoplasms, and 15% had dose-limiting toxicities. The 6.0 GBq cohort was closed and 4.5 GBq per cycle recommended (Wild 2024, Eur J Nucl Med Mol Imaging; published online 2023). A follow-up dosimetry paper from the same trial described tumour and organ doses (2024, Eur J Nucl Med Mol Imaging) †. [5]

Earlier Phase 1 with unexpected haematotoxicity

A US Phase 1 of Lu-177 DOTA-JR11 was halted after grade 4 haematological toxicity in 4 of 7 patients following a second cycle, which led to the lower-activity design of the later study (Reidy-Lagunes 2019, Clin Cancer Res). [4]

Ga-68 satoreotide trizoxetan PET vs Ga-68 DOTATOC

A Phase I/II in 12 patients with GEP-NETs found the antagonist detected more liver lesions (sensitivity 94% vs 59% in one reading) with higher tumour-to-liver ratios than Ga-68 DOTATOC (Nicolas 2018, J Nucl Med). [3]
Graded B (very small)

Pilot comparison with Lu-177 DOTATATE

An intra-patient comparison in four patients showed 1.7–10-fold higher tumour dose with Lu-177 DOTA-JR11 than with Lu-177 DOTATATE (Wild 2014, J Nucl Med). [2]

Human data in other SSTR-positive cancers

Preclinical rationale only; no published trials.

4Reported side effects and interactions

Literature-reported

haematological toxicity is the defining issue — lymphopenia, thrombocytopenia and neutropenia at grade 3–4 rates well above those seen with Lu-177 DOTATATE at comparable activity; two therapy-related myeloid neoplasms in 40 patients. No grade 3–4 kidney toxicity reported at 4.5 GBq with amino-acid protection. Nausea and fatigue as for other PRRT. One death after a dose-limiting toxicity in a patient with prior chemotherapy was judged unlikely to be related.

Community-reported

Community use. essentially none documented.

Theoretical. antagonists lack octreotide's hormone-suppressing effect, so hormonal flare in functional tumours could in principle differ from PRRT; not characterised.

Interactions. somatostatin analogue is still used before imaging, though antagonists may be less affected by receptor occupancy than agonists (small study evidence).

Markers researchers commonly monitor

Taken from the trial protocols; relevant only to patients in studies:

MarkerWhy it's watched
CBC with differential, repeated frequently after each cyclehaematological toxicity was dose-limiting, and lymphocyte and platelet nadirs drove dose modification.
Bone-marrow dosimetry (blood-based and imaging-based)a 1.5 Gy marrow limit was built into the protocol.
Kidney dosimetry, creatinine/eGFR23 Gy kidney limit; amino-acid co-infusion used.
Chromogranin A and relevant hormonesbiochemical response.
Ga-68 antagonist PETfor selection and response.

Free for everyone. Safety information is never behind a paywall.


5Reconstitution and handling

Not applicable to individuals. Prepared only in trial-site radiopharmacies under investigational protocols. No calculator link is provided for this compound.


6Commonly studied alongside

DOTATATE (#201) and DOTATOC (#202) as the agonist comparators; octreotide (#124); other antagonist ligands (LM3, Cu-64/Ga-68 NODAGA-LM3) that have continued in academic studies after the sponsored satoreotide programme.

Informational cross-links. Not stack recommendations.


7Regulatory status by region

RegionStatus (checked —)
United StatesNot FDA-approved; investigational (orphan designation held †)
European UnionNot authorised; investigational
United KingdomNot licensed
AustraliaNot approved; Australian centres participated in the Phase I/II
South AfricaNot registered
Sport (WADA)Not listed

8Open questions

  • Can activity, peptide mass or cycle scheduling be tuned so that the higher tumour dose is kept while marrow toxicity falls to agonist-like levels?
  • Does the antagonist approach translate into better PFS or survival than Lu-177 DOTATATE in a randomised trial? None exists.
  • Whether antagonist PET (satoreotide or LM3) will be developed to registration as an imaging agent.
  • Future of the programme after the sponsored Phase I/II †.

9References

  1. 1Ginj M et al. (2006). Radiolabeled somatostatin receptor antagonists are preferable to agonists for in vivo peptide receptor targeting of tumors. Proc Natl Acad Sci USA. PubMed · DOI
  2. 2Wild D et al. (2014). Comparison of somatostatin receptor agonist and antagonist for peptide receptor radionuclide therapy: a pilot study. J Nucl Med. PubMed · DOI
  3. 3Nicolas GP et al. (2018). Sensitivity comparison of 68Ga-OPS202 and 68Ga-DOTATOC PET/CT in patients with gastroenteropancreatic neuroendocrine tumors: a prospective phase II imaging study. J Nucl Med. PubMed · DOI
  4. 4Reidy-Lagunes D et al. (2019). Phase I trial of well-differentiated neuroendocrine tumors (NETs) with radiolabeled somatostatin antagonist 177Lu-satoreotide tetraxetan. Clin Cancer Res. PubMed · DOI
  5. 5Wild D et al. (2024). A phase I/II study of the safety and efficacy of [177Lu]Lu-satoreotide tetraxetan in advanced somatostatin receptor-positive neuroendocrine tumours. Eur J Nucl Med Mol Imaging. PubMed · DOI
  6. 6Fani M, Nicolas GP, Wild D (2017). Somatostatin receptor antagonists for imaging and therapy. J Nucl Med. PubMed · DOI

† Being confirmed by our reviewers against current sources.


10Community

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Self-reported side effects Phase 2

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11Page history

31 Oct 2026Profile published — awaiting medical review

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Satoreotide: what the research shows · Research Protocol Builder