Zadavotide Guraxetan
The 'imaging and therapy' PSMA ligand behind many hospital-made lutetium-177 treatments for prostate cancer
Zadavotide guraxetan is the official name of PSMA I&T, a small molecule that latches onto a protein found in large amounts on prostate cancer cells. Hospitals attach a radioactive metal to it: gallium-68 or copper-64 to see the cancer on a PET scan, or lutetium-177 to irradiate it from the inside. It has been given to many men in Europe, Australia and Asia, often as a hospital-made preparation, and phase 3 trials have reported, but no regulator has approved it. It is not something anyone can buy.
Used in human trials: 7.4 GBq, Every 6 to 8 weeks, Intravenous (Lutetium-177 PSMA I&T, late-stage mCRPC (100 men)) 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?
A radioligand is a two-part drug. One part is a molecule that seeks out a target on cancer cells; the other is a radioactive atom held on to it. If the atom gives off positrons, a PET camera can show where the drug has gathered, and the scan maps the cancer. If it gives off beta or alpha particles, the radiation damages cells within a few millimetres of where the drug sits, so the same targeting molecule becomes a treatment. Using one molecule for both jobs is called theranostics.
Zadavotide guraxetan is the international nonproprietary name of PSMA I&T, short for 'imaging and therapy'. Its targeting part is a small urea-based molecule built from glutamate and lysine that fits the active site of prostate-specific membrane antigen (PSMA), an enzyme carried in large amounts on most metastatic prostate cancers. A DOTAGA ring holds the metal. Munich researchers described it in 2015: in mice it went mainly to PSMA-positive tumours and the kidneys, gallium-68 PSMA I&T PET showed bone, lymph node and liver spread in patients, and the first two men treated with the lutetium-177 version had no detectable side effects.
In practice it became one of the two workhorse ligands for PSMA radioligand therapy, alongside PSMA-617, the ligand in the approved drug Pluvicto. Centres in Europe, Australia and Asia have published series with it, and some make it in their own radiopharmacies, as the 2026 German comparison describes. Head-to-head series have found the two ligands broadly alike: in a German group of 138 men, lutetium-177 PSMA I&T cleared from the body faster (whole-body half-life 35 hours against 42), gave the kidneys a slightly higher dose and delivered a similar dose to tumours; a matched comparison of 110 men and a 2026 propensity-matched study of 140 found no meaningful difference in survival.
Most of the evidence comes from men with metastatic castration-resistant prostate cancer whose disease had grown despite hormone drugs and chemotherapy. In the largest early series, 100 such men in Munich received up to six cycles of 7.4 GBq: 38 had their PSA fall by half or more, median survival was 12.9 months, and serious blood count drops were uncommon. Later work moved it earlier. The LUNAR trial at UCLA gave two cycles before targeted radiotherapy in men with a few hormone-sensitive metastases and, in its published results, more than doubled the time before the cancer progressed. It is also being combined with radium-223 and capecitabine and has been labelled with other isotopes, actinium-225 and terbium-161, in early trials.
Regulators have not approved it anywhere. Two companies took it into phase 3: the SPLASH trial of the version Lantheus called PNT2002, and Curium's ECLIPSE trial, which the company reported in November 2024 had met its main goal of delaying radiographic progression against a switch of hormone drug. Lantheus's 2025 annual report says the survival results of SPLASH were confounded because most control patients crossed over to the drug, and that it does not plan to file for approval. Curium has said it is working with FDA on a submission plan and in 2026 announced an accepted application for a phase 3 trial in China and the first patient in a registrational trial in Japan. Drugs@FDA and the European Medicines Agency hold no record.
It is a hospital radiopharmaceutical. It is made shortly before use, handled only by nuclear medicine staff under radiation licences, and given by intravenous injection to selected patients whose PSMA PET scan shows enough uptake. There is no form of it for personal use and nothing to buy.
Mechanism of Action
PSMA I&T binds prostate-specific membrane antigen on the cell surface, is taken inside the cell, and carries whatever radioactive metal its chelator holds.
Beta radiation from lutetium-177
Bound and internalised, lutetium-177 releases beta particles that travel a few millimetres, damaging the DNA of the cancer cell and its neighbours.
Imaging with gallium-68 or copper-64
With a positron-emitting metal in the same chelator, a PET scan shows where PSMA-positive disease is and whether therapy is likely to reach it.
Kidney and gland exposure
PSMA in the kidneys, salivary and lacrimal glands also takes it up, which is why dry mouth and kidney dose are the main safety concerns (dosimetry studies).
Published Research
Studies of PSMA I&T itself, read from their PubMed abstracts: first human use, dosimetry, large treatment series, comparisons with PSMA-617, randomised and phase 1/2 trials, and imaging. Studies that used the same ligand with a different radioactive metal (copper-64, actinium-225, terbium-161) are included and say so. The main LUNAR paper names the drug only as lutetium-177 PSMA in its title and is listed under References.
Design and first patients
Munich chemists built PSMA I&T for both imaging and therapy; it bound PSMA at nanomolar strength and went mainly to tumours and kidneys in mice. Gallium-68 PSMA I&T PET showed bone, lymph node and liver metastases with high contrast, and two men treated with the lutetium-177 version had no detectable side effects.
Organ and tumour doses
Across 34 cycles in 18 men, the kidneys received about 0.72 Gy per GBq, the parotid glands 0.55 and the lacrimal glands 3.8; tumours received 3.2 Gy per GBq on average, with doses falling slightly over four cycles. Uptake on the pre-treatment PET scan moderately predicted the tumour dose.
100 men with late-stage disease
Under compassionate use, 100 heavily pretreated men received 7.4 GBq every 6 to 8 weeks (319 cycles). PSA fell by at least half in 38, median clinical progression-free survival was 4.1 months and overall survival 12.9 months; grade 3/4 anaemia (9%), low platelets (4%) and low neutrophils (6%) were the main toxicities. Liver or lung metastases and rising LDH predicted worse results.
Side by side with PSMA-617
In 138 men (51 given a mean 6.1 GBq of lutetium-177 PSMA I&T, 87 given PSMA-617), PSMA I&T had a shorter whole-body half-life (35 vs 42 hours), a higher kidney dose (0.92 vs 0.77 Gy per GBq) and a similar tumour dose. Neither caused kidney damage; small falls in blood counts needed no treatment.
Matched-pair comparison
Two centres matched 55 men on PSMA I&T with 55 on PSMA-617. Grade 3 anaemia occurred in 1 against 5, no other grade 3/4 toxicity was seen, and median survival did not differ (12 vs 13 months).
Survival against the approved ligand
In a propensity-matched single-centre study of 140 chemotherapy-pretreated men, in-house lutetium-177 PSMA I&T (6.0 GBq every 8 weeks) and commercial PSMA-617 (7.4 GBq every 6 weeks) gave similar median survival (14 vs 15 months). PSMA-617 produced deeper PSA falls, which the authors linked to its higher total activity.
Kidney and blood safety
In 49 men given at least three cycles, no grade 3/4 blood or kidney toxicity occurred. Mild kidney changes depended on the measure used (22% by creatinine, 67% by eGFR), and many patients already had reduced kidney function or white cells before starting.
Men aged 75 and over
Fifty-six men aged 75 to 95 had no grade 3 or worse toxicity. Median survival was 11 months; any PSA fall predicted longer survival (21 vs 7 months), and liver metastases shorter survival.
SPLASH lead-in cohort
Before the randomised phase 3 SPLASH trial, 27 men who had progressed on one hormone drug and had no chemotherapy received up to four cycles of 6.8 GBq of the version called PNT2002. Dry mouth (22%, all mild), fatigue and nausea were the commonest related effects, PSA halved in 42% and median radiographic progression-free survival was 11.5 months.
LUNAR trial dosimetry
In the 45 men randomised to two 6.8 GBq cycles before stereotactic radiotherapy for a few hormone-sensitive metastases, organ doses were low (kidneys 0.35, lacrimal glands 0.70 Gy per GBq). The parent trial reported longer PSMA-PET-based progression-free survival than radiotherapy alone.
Combined with radium-223 (AlphaBet)
In a phase 1/2 trial in Melbourne, 36 men received 7.4 GBq of lutetium-177 PSMA I&T with radium-223 every 6 weeks. There were no dose-limiting toxicities, PSA fell by half in 55% of 33 evaluable patients, and 14% had grade 3 or worse related events, mainly anaemia and neutropenia.
Terbium-161 version (VIOLET)
The same ligand carrying terbium-161, which adds very short-range Auger electrons, was escalated to 7.4 GBq in 30 men with no dose-limiting toxicity. Only two grade 3 related events occurred (pain and lymphopenia) and no one stopped for toxicity.
Actinium-225 version, phase 1
Nine men received two cycles of actinium-225 PSMA I&T at 8 to 12 MBq. Dry mouth affected 89%; two dose-limiting toxicities at 12 MBq set a recommended dose of 10 MBq, and PSA halved in 4 of 9.
Gallium-68 PET for staging
In 82 men with newly diagnosed prostate cancer, gallium-68 PSMA I&T PET found disease in 83% and spread beyond the prostate only in intermediate- and high-risk cases. Against surgery in 40 men, it detected lymph node metastases with 35% sensitivity and 98% specificity.
Copper-64 labelling
PSMA I&T labelled with copper-64 stayed over 90% intact in serum for 60 hours and bound PSMA-positive cells 7.5 times more than negative ones; in mice, tumour uptake rose to a peak at 48 hours while kidney uptake fell, supporting human trials.
Dosing Data
PSMA I&T has no approved label anywhere. The rows below are administered activities, the amount of radioactivity injected, as given in the published human studies carded above. They are measured in gigabecquerels (GBq) or megabecquerels (MBq), not milligrams.
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.
What a Buyer Needs to Know
What is sold, how it is mixed, stored and taken, and what is known about its safety, quality and legal status. Each part names its source. Where we have none, it says unknown.
What is sold
Unknown: we hold no regulator's label that says in what form Zadavotide Guraxetan is supplied. It is a radioactive drug: the next part says where it is prepared and given.
Mixing a vial: a worked example
Nothing to mix at home, and no syringe units to work out: Zadavotide Guraxetan is a radioactive drug, prepared and given in nuclear-medicine departments, and its dose is an amount of radioactivity (MBq or GBq), not a weight.
This page's dosing note: “PSMA I&T is dosed by radioactivity and prepared in a hospital radiopharmacy shortly before injection; no reconstitution maths applies.”
Source: this page's own note in Dosing Data below; the amount of each dose row in Dosing Data below.
Storage before and after mixing
Unknown: no label on file says how Zadavotide Guraxetan is stored. It is a radioactive drug held by the nuclear-medicine department that prepares and gives it (see the part above); the home rules for a mixed vial in the mixing guide do not apply to it.
How it is taken
As it was given in human studies: Intravenous (Every 6 to 8 weeks; Lutetium-177 PSMA I&T, late-stage mCRPC (100 men)).
Source: Used in human trials: the route and frequency of each row in Dosing Data below.
What to expect, and when
How long it stays in the body: not established by a measurement cited on this entry.
How long the doses were given: Lutetium-177 PSMA I&T, late-stage mCRPC (100 men): Up to 6 cycles; Lutetium-177 PNT2002, SPLASH lead-in (27 men): Up to 4 cycles; Lutetium-177 PSMA I&T before radiotherapy, LUNAR (45 men): Before stereotactic radiotherapy.
When effects appear: unknown; no source on this page gives a time to effect for Zadavotide Guraxetan. Results reported in the studies are under Published Research.
Source: Used in human trials, the duration of each row in Dosing Data below.
Side effects, and when to stop or get help
From the Side Effects section: Dry mouth, from uptake in the salivary glands (22% of the SPLASH lead-in cohort, all mild); Fatigue and nausea; Falls in blood counts: grade 3/4 anaemia in 9%, low platelets in 4% and low neutrophils in 6% of 100 late-stage patients; Radiation dose to the kidneys and lacrimal glands, watched in dosimetry studies; no kidney damage was seen in the 51-patient comparison. Full list and cautions ↓
When to stop or get help: unknown; no label or trial on file sets rules for stopping Zadavotide Guraxetan. Treat a severe or unexpected reaction as a reason to stop and see a doctor.
Source: the Side Effects section below (“From the studies above”).
Interactions
Unknown: a PubMed search for human interaction studies of Zadavotide Guraxetan (reviewed 2026-10-28) found none. Unknown is not the same as safe to combine.
Every peptide's record, with its source: the interaction matrix.
Checking what you bought
Unknown: no published independent test of Zadavotide Guraxetan products is in our lab-results database yet, so how products sold under this name measure up is not known.
To read a certificate of analysis, paste it into the COA decoder; it checks the measured mass against Zadavotide Guraxetan's expected mass, 1,498.4 Da, from this entry's molecular data. Trust & Verification explains what independent testing can and cannot show.
Legal status
US: In Clinical Trials (Not approved: no Drugs@FDA record (openFDA, searched October 29, 2026) and none in the EMA medicines list). Sport: Prohibited (S0 catch-all).
Country by country ↓ · Regulatory tracker
Source: this entry's approval status and the WADA Prohibited List, as in Legal Status below.
Side Effects & Contraindications
Reported Side Effects
From the studies above.
Contraindications & Cautions
There is no approved label, so there are no official contraindications. Points from the studies above:
Legal Status
Zadavotide guraxetan is not approved by any regulator checked. It is made and given in hospitals under investigational, compassionate-use or local pharmacy rules.
Frequently Asked Questions
?What is zadavotide guraxetan?
The official generic name of PSMA I&T, a small molecule that binds the PSMA protein on prostate cancer cells. With a radioactive metal attached it is used either to image the cancer or to treat it with radiation from inside the body.
?Is it approved?
No. Phase 3 trials have reported, and one company says it is working with FDA on a submission, but no regulator has approved it. It is given in hospitals under trial, compassionate-use or local pharmacy rules.
?How does it differ from Pluvicto?
Pluvicto is lutetium-177 attached to a different PSMA ligand, PSMA-617. The two behave much alike: comparison studies found similar tumour doses and survival, with PSMA I&T clearing a little faster and giving the kidneys a slightly higher dose.
?What does treatment involve?
An intravenous injection of about 6 to 7.4 GBq of lutetium-177 PSMA I&T in a nuclear medicine unit, repeated every 6 to 8 weeks for up to four to six cycles in the studies, with blood counts and kidney function checked between doses.
?Can I buy it?
No. It is a radioactive drug made in hospital radiopharmacies shortly before use and given only by licensed nuclear medicine staff. There is no form of it for personal use.
References
- [other] PubChem CID 156596528, Zadavotide guraxetan: formula C63H92IN11O23, molecular weight 1498.4. Read October 28, 2026. https://pubchem.ncbi.nlm.nih.gov/compound/156596528
- [registry] ClinicalTrials.gov API v2, read October 28, 2026: NCT06235099 (phase 3, copper-64 PSMA I&T PET imaging, completed); NCT04647526 (SPLASH, phase 3, lutetium-177 PNT2002); NCT05204927 (ECLIPSE, phase 3, lutetium-177 PSMA I&T); NCT05496959 (LUNAR, phase 2).
- [other] Lantheus Holdings, Form 10-K for fiscal year 2025 (SEC EDGAR, filed 2026): SPLASH reached all prespecified overall survival events, results confounded by crossover; the company does not currently plan to pursue an NDA for PNT2002. Read October 29, 2026.
- [other] Curium, press release, January 7, 2026: China's Center for Drug Evaluation accepted the IND for 177Lu-PSMA-I&T in mCRPC (phase 3 bridging trial). Read October 29, 2026.
- [other] Urology Times, November 13, 2024, reporting Curium's release: the phase 3 ECLIPSE trial (NCT05204927) of 177Lu-PSMA-I&T against a change of hormone therapy met its radiographic progression-free survival endpoint; Curium will work with FDA on a submission plan. Read October 29, 2026.
- [other] US FDA, Drugs@FDA (openFDA): no application for zadavotide or PSMA I&T. European Medicines Agency medicines list: no record. Searched October 29, 2026.
- [pubmed] Weineisen M, et al. "68Ga- and 177Lu-Labeled PSMA I&T: Optimization of a PSMA-Targeted Theranostic Concept and First Proof-of-Concept Human Studies." J Nucl Med, 2015;56(8):1169-76. PMID: 26089548.
- [pubmed] Okamoto S, et al. "Radiation Dosimetry for (177)Lu-PSMA I&T in Metastatic Castration-Resistant Prostate Cancer: Absorbed Dose in Normal Organs and Tumor Lesions." J Nucl Med, 2017;58(3):445-450. PMID: 27660138.
- [pubmed] Heck MM, et al. "Treatment Outcome, Toxicity, and Predictive Factors for Radioligand Therapy with (177)Lu-PSMA-I&T in Metastatic Castration-resistant Prostate Cancer." Eur Urol, 2019;75(6):920-926. PMID: 30473431.
- [pubmed] Schuchardt C, et al. "Prostate-Specific Membrane Antigen Radioligand Therapy Using (177)Lu-PSMA I&T and (177)Lu-PSMA-617 in Patients with Metastatic Castration-Resistant Prostate Cancer: Comparison of Safety, Biodistribution, and Dosimetry." J Nucl Med, 2022;63(8):1199-1207. PMID: 34887335.
- [pubmed] Hartrampf PE, et al. "Matched-pair analysis of [(177)Lu]Lu-PSMA I&T and [(177)Lu]Lu-PSMA-617 in patients with metastatic castration-resistant prostate cancer." Eur J Nucl Med Mol Imaging, 2022;49(9):3269-3276. PMID: 35243517.
- [pubmed] Hasenauer N, et al. "Overall Survival with [(177)Lu]Lu-PSMA-617 Versus [(177)Lu]Lu-PSMA I&T: A Propensity Score-Matched Real-World Analysis." J Nucl Med, 2026;67(9):1440-1447. PMID: 42392698.
- [pubmed] Hartrampf PE, et al. "Hematotoxicity and Nephrotoxicity in Prostate Cancer Patients Undergoing Radioligand Therapy with [(177)Lu]Lu-PSMA I&T." Cancers (Basel), 2022;14(3). PMID: 35158913.
- [pubmed] Schwinger M, et al. "Radioligand treatment with [(177)Lu]Lu-PSMA I&T in elderly Patients - Safety, efficacy, and prognostic factors for survival." Eur J Nucl Med Mol Imaging, 2026;53(3):1469-1478. PMID: 40851054.
- [clinical-trial] Hansen AR, et al. "Initial clinical experience with [(177)Lu]Lu-PNT2002 radioligand therapy in metastatic castration-resistant prostate cancer: dosimetry, safety, and efficacy from the lead-in cohort of the SPLASH trial." Front Oncol, 2024;14:1483953. PMID: 39839782.
- [clinical-trial] Ells Z, et al. "Dosimetry Analysis of (177)Lu-PSMA-I&T in Patients with Low-Volume Oligometastatic Hormone-Sensitive Prostate Cancer: A Secondary Analysis of the LUNAR Trial." J Nucl Med, 2026;67(7):1125-1131. PMID: 41927282.
- [clinical-trial] Kostos L, et al. "Lutetium-177 [(177)Lu]Lu-PSMA-I&T plus radium-223 in patients with metastatic castration-resistant prostate cancer (AlphaBet): an interim analysis of the investigator-initiated, single-centre, single-arm, phase 1/2 trial." Lancet Oncol, 2025;26(11):1479-1488. PMID: 41119954.
- [clinical-trial] Buteau JP, et al. "First-in-human results of terbium-161 [(161)Tb]Tb-PSMA-I&T dual beta-Auger radioligand therapy in patients with metastatic castration-resistant prostate cancer (VIOLET): a single-centre, single-arm, phase 1/2 study." Lancet Oncol, 2025;26(8):1009-1017. PMID: 40617237.
- [clinical-trial] Ling SW, et al. "Phase 1 Dose-Escalation Study of [(225)Ac]Ac-PSMA I&T in Patients with Metastatic Castration-Resistant Prostate Cancer: An Analysis of Safety, Tolerability, and Dosimetry." J Nucl Med, 2026;67(7):1109-1116. PMID: 42020144.
- [pubmed] Cytawa W, et al. "(68)Ga-PSMA I&T PET/CT for primary staging of prostate cancer." Eur J Nucl Med Mol Imaging, 2020;47(1):168-177. PMID: 31529265.
- [pubmed] Lee CH, et al. "The Feasibility of (64)Cu-PSMA I&T PET for Prostate Cancer." Cancer Biother Radiopharm, 2022;37(6):417-423. PMID: 33434438.
- [clinical-trial] Kishan AU, et al. "(177)Lu-Prostate-Specific Membrane Antigen Neoadjuvant to Stereotactic Ablative Radiotherapy for Oligorecurrent Prostate Cancer (LUNAR): An Open-Label, Randomized, Controlled, Phase II Study." J Clin Oncol, 2025;43(36):3812-3821. PMID: 41223345.
Sources & Citations
Studies were read from their PubMed abstracts on October 29, 2026; regulatory status from Drugs@FDA (openFDA), the EMA medicines list, Lantheus's 2025 Form 10-K and Curium's press releases, read October 29, 2026. The formula is PubChem's.
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. Talk to a licensed clinician about your own situation.