RPB

PSMA-617 and PSMA-11

PSMA-617 = vipivotide tetraxetan; Lu-177 PSMA-617 = Pluvicto, lutetium Lu 177 vipivotide tetraxetan; PSMA-11 = gozetotide, HBED-CC-PSMA; Ga-68 PSMA-11 = Locametz, Illuccix, gallium Ga 68 gozetotide; related: PSMA-1007, piflufolastat F-18 (Pylarify), flotufolastat F-18 (Posluma), Ac-225 PSMA-617

Oncology & imaging
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Note on this profile. These are approved prescription radiopharmaceuticals handled only in licensed nuclear-medicine departments. This page explains the published science. There is no community or self-directed use.

1What it is

PSMA (prostate-specific membrane antigen) is a protein on the surface of prostate cells that is produced at much higher levels by prostate cancer, especially as the disease advances. It is also an enzyme (glutamate carboxypeptidase II), and that enzymatic pocket is what these ligands exploit. German groups in Heidelberg developed PSMA-11 in 2012 as a Ga-68 PET tracer, then PSMA-617 in 2015 with a DOTA chelator so that lutetium-177 could be attached for therapy.

Unlike DOTATATE, these are not derived from a natural hormone. The glutamate and lysine are linked by a urea group that locks into the enzyme's active site; the "peptide-like" character is why they appear in peptide radiopharmaceutical reviews, but they are more accurately described as small-molecule peptidomimetics. Ga-68 PSMA-11 was approved in the US in December 2020 (academic NDAs) with commercial kits (Illuccix, Locametz) following in 2021–2022. Pluvicto was approved in March 2022.

2How it's thought to work

Targeting. nanomolar binding to PSMA's active site, followed by receptor-mediated internalisation. PSMA is expressed 100–1,000 times more on prostate cancer cells than on normal prostate; it also appears at lower levels on salivary glands, kidney proximal tubules, small intestine and the neovasculature of some other tumours, which explains the main side effects.
Imaging. Ga-68 positron emission maps PSMA-expressing lesions with higher sensitivity than CT and bone scan, particularly at low PSA levels after relapse.
Therapy. Lu-177 beta particles (~2 mm range) deliver cell-killing dose to the tumour. A Ga-68 (or F-18) PSMA PET scan is required first to confirm the tumour takes up the ligand ("PSMA-positive").
Why some tumours fail. heterogeneous or lost PSMA expression, very bulky disease, and neuroendocrine dedifferentiation reduce uptake and response.
A urea-based ligand of prostate-specific membrane antigen with a chelator attached. PSMA is expressed far more densely on prostate cancer than on normal tissue; gallium-68 makes it visible, lutetium-177 irradiates it from within.Schematic — not to scale

3What the research shows

Lu-177 PSMA-617 after chemotherapy (VISION)

VISION randomised 831 men with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) previously treated with an androgen-receptor pathway inhibitor and taxane chemotherapy to Pluvicto plus standard care or standard care alone. Radiographic PFS was 8.7 vs 3.4 months (HR 0.40) and overall survival 15.3 vs 11.3 months (HR 0.62) (Sartor 2021, NEJM). [3]

Lu-177 PSMA-617 before chemotherapy (PSMAfore)

PSMAfore (n=468) compared Pluvicto with switching to a second androgen-receptor pathway inhibitor in taxane-naive mCRPC. Median rPFS was 9.3 vs 5.6 months (HR 0.41); overall survival did not reach significance (HR 0.91), with 60% of the control arm crossing over (Morris 2024, Lancet). US approval was extended to this pre-chemotherapy setting in March 2025. [4]

Lu-177 PSMA-617 vs cabazitaxel (TheraP)

An Australian randomised Phase 2 (n=200) found higher PSA-50 response with Lu-177 PSMA-617 (66% vs 37%) and fewer grade 3–4 adverse events than cabazitaxel, with no overall-survival difference (Hofman 2021, Lancet; Hofman 2024, Lancet Oncol follow-up). [5]
Graded A (recently reported)

Hormone-sensitive disease (PSMAddition)

A Phase 3 in metastatic hormone-sensitive prostate cancer reported a positive rPFS result in 2025 †.

Ga-68 PSMA-11 PET for staging and biochemical recurrence

proPSMA (n=302) randomised men with high-risk disease before surgery or radiotherapy to PSMA PET/CT or conventional CT plus bone scan; accuracy was 92% vs 65% (Hofman 2020, Lancet). Prospective multicentre data in biochemical recurrence showed detection rates rising with PSA level and a positive predictive value around 84–92% (Fendler 2019, JAMA Oncol). These trials underpin the approvals. [6][7]

Actinium-225 PSMA-617

Case series in patients who failed Lu-177 report responses from the alpha-emitter at the cost of severe dry mouth (Kratochwil 2016, J Nucl Med). Randomised trials are under way. [8]

4Reported side effects and interactions

Literature-reported

Literature (Pluvicto). dry mouth (xerostomia, ~39% in VISION; caused by PSMA on salivary glands), fatigue (~43%), nausea (~35%), anaemia, thrombocytopenia, lymphopenia (grade ≥3 haematological events in roughly 20–25%), reduced appetite, constipation, vomiting. Kidney function decline is uncommon but monitored; acute kidney injury has been reported. Rare secondary myeloid neoplasms. Radiation safety precautions for contacts for several days.

Literature (Ga-68 PSMA-11). no clinically significant adverse reactions beyond the small radiation dose; occasional nausea, headache or taste change. Main diagnostic pitfall is false-positive uptake in non-prostatic tissues (ganglia, healing fractures, some benign lesions) and in other tumours whose blood vessels express PSMA.

Community-reported

Community use. essentially none documented.

Theoretical. infertility from gonadal dose; the label advises effective contraception during treatment and for months after.

Interactions. androgen-deprivation therapy is continued; whether it raises PSMA expression and uptake is under study. Avoid other myelosuppressive therapy close to a cycle. Contrast agents and recent chemotherapy can confound PET reading.

Markers researchers commonly monitor

From the Pluvicto label and VISION/PSMAfore protocols:

MarkerWhy it's watched
PSAthe disease marker; a ≥50% fall is the standard response measure, with the caveat that PSA can rise transiently early on.
CBC before every cyclemarrow suppression is the dose-limiting toxicity; delayed myeloid neoplasms are a class risk.
Creatinine/eGFR and electrolytesrenal PSMA expression plus excretion through the kidney; hydration is encouraged.
Liver enzymesliver metastases and treatment effects.
PSMA PET before treatment (eligibility) and to assess response or heterogeneity; FDG PET is sometimes added to detect PSMA-negative disease
Alkaline phosphatase and LDHprognostic markers in mCRPC used in trial stratification.
Salivary function and weightdry mouth and appetite loss affect quality of life and are tracked clinically.

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

5Reconstitution and handling

Not applicable to individuals. Illuccix and Locametz are kits labelled with generator Ga-68 by a hospital radiopharmacy; Pluvicto arrives as a ready-to-infuse shielded vial calibrated to 7.4 GBq. No calculator link is provided for this compound.

6Commonly studied alongside

Androgen-receptor pathway inhibitors (enzalutamide, abiraterone) as backbone or comparator; taxanes (docetaxel, cabazitaxel) as sequence or comparator; PARP inhibitors and immunotherapy in combination trials; DOTATATE (#201) is the model theranostic pair the PSMA programme followed.

Informational cross-links. Not stack recommendations.

7Regulatory status by region

RegionStatus (checked —)
United StatesGa-68 PSMA-11 FDA-approved December 2020 (academic), Illuccix December 2021, Locametz March 2022. Pluvicto FDA-approved March 2022 (post-ARPI, post-taxane mCRPC), expanded March 2025 to taxane-naive mCRPC after ARPI
European UnionLocametz EMA-authorised December 2022; Pluvicto authorised December 2022 for PSMA-positive mCRPC after ARPI and taxane; pre-taxane extension †
United KingdomPluvicto MHRA-licensed; NICE guidance on access †. PSMA PET widely used in NHS with several Ga-68 and F-18 tracers
AustraliaPluvicto TGA-registered (2022–2023 †); PSMA PET MBS-funded since 2022; Australia ran TheraP and proPSMA
South AfricaPluvicto registration status †; Lu-177 PSMA therapy and Ga-68 PSMA PET offered at academic and some private centres under access schemes
Sport (WADA)Not listed; cancer treatment with no performance relevance

8Open questions

  • Whether moving Lu-177 PSMA-617 into hormone-sensitive or even localised disease improves survival, not just rPFS.
  • Alpha-emitters (Ac-225) versus beta-emitters, and how to protect the salivary glands.
  • Predicting non-responders: the role of PSMA/FDG mismatch and tumour heterogeneity.
  • Retreatment, dosimetry-personalised activity, and the long-term rate of secondary myeloid cancers.

9References

  1. 1Eder M et al. (2012). 68Ga-complex lipophilicity and the targeting property of a urea-based PSMA inhibitor for PET imaging. Bioconjug Chem. PubMed · DOI
  2. 2Benešová M et al. (2015). Preclinical evaluation of a tailor-made DOTA-conjugated PSMA inhibitor with optimized linker moiety for imaging and endoradiotherapy of prostate cancer (PSMA-617). J Nucl Med. PubMed · DOI
  3. 3Sartor O et al. (2021). Lutetium-177-PSMA-617 for metastatic castration-resistant prostate cancer (VISION). N Engl J Med. PubMed · DOI
  4. 4Morris MJ et al. (2024). 177Lu-PSMA-617 versus a change of androgen receptor pathway inhibitor therapy for taxane-naive patients with progressive metastatic castration-resistant prostate cancer (PSMAfore). Lancet. DOI
  5. 5Hofman MS et al. (2021). [177Lu]Lu-PSMA-617 versus cabazitaxel in patients with metastatic castration-resistant prostate cancer (TheraP). Lancet. PubMed
  6. 6Hofman MS et al. (2020). Prostate-specific membrane antigen PET-CT in patients with high-risk prostate cancer before curative-intent surgery or radiotherapy (proPSMA). Lancet. PubMed · DOI
  7. 7Fendler WP et al. (2019). Assessment of 68Ga-PSMA-11 PET accuracy in localizing recurrent prostate cancer: a prospective single-arm clinical trial. JAMA Oncol. PubMed · DOI
  8. 8Kratochwil C et al. (2016). 225Ac-PSMA-617 for PSMA-targeted α-radiation therapy of metastatic castration-resistant prostate cancer. J Nucl Med. PubMed · DOI
  9. 9FDA. Pluvicto prescribing information (2025 revision); Locametz and Illuccix prescribing information. FDA news release, 28 March 2025: expansion of Pluvicto indication. PubMed

References are being resolved to PubMed/DOI identifiers; links search PubMed for the citation until then.

† Being confirmed by our reviewers against current sources.

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11Page history

31 Oct 2026Profile published — awaiting medical review

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