PSMA I&S
The technetium-99m PSMA tracer built so a surgeon's gamma probe can find prostate cancer in lymph nodes, and what the trials of that surgery show
PSMA I&S ('imaging and surgery') is a small molecule that binds prostate-specific membrane antigen, a protein made in large amounts by prostate cancer cells. Labelled with technetium-99m, the workhorse isotope of nuclear medicine, it is injected the day before an operation, a SPECT/CT scan shows where it has gathered, and in theatre a gamma probe picks up the radioactive lymph nodes so they can be removed. It is also used on its own as a SPECT scan where PSMA PET is not available. It is not approved anywhere; it is made in hospital radiopharmacies for trials and local use.
Used in human trials: 717 MBq (range 562-828 MBq), Single injection, Intravenous (Dosimetry in healthy volunteers (4 people)) 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?
Prostate-specific membrane antigen (PSMA) is an enzyme on the surface of prostate cells, and most prostate cancers make far more of it than normal tissue does. Small molecules that grip PSMA can carry a radioactive atom to the cancer. With a positron emitter such as gallium-68 or fluorine-18 they become PSMA PET scans. PSMA I&S is the same idea built for technetium-99m, a gamma-emitting isotope that is cheaper and more widely available than the PET isotopes and better suited to handheld gamma probes.
It was designed as a cheaper alternative to an indium-111 tracer, PSMA I&T, that surgeons had been using to find small cancer deposits during operations. The 2017 paper that introduced it compared two versions of the metal-holding chelator, chose the one built from D-serines because it entered cells better and was more stable in the body, and showed that it could be labelled from a simple kit in more than fifty preparations with at least 98% purity. In the first patients it cleared slowly from the blood, because about 94% of it binds to plasma proteins, but that slowness let it keep collecting in tumours, so the contrast between cancer and background kept rising for about 21 hours.
That timing suits surgery. The usual protocol injects the tracer the afternoon or evening before the operation, takes a SPECT/CT scan to confirm that the lesions seen on PSMA PET have taken it up, and then operates the next day. In theatre the surgeon passes a gamma probe over the tissue; lymph nodes holding cancer give a higher count than their surroundings and are cut out, and the removed tissue can be checked again outside the body. Since 2022 a miniature 'DROP-IN' probe that a surgical robot can pick up has made the method work in robot-assisted keyhole surgery as well as open operations.
Two kinds of patient have been studied. In recurrent disease, men whose PSA has risen again after prostatectomy or radiotherapy and whose PSMA PET shows a few pelvic nodes, PSMA-guided salvage surgery tries to remove those nodes and delay further treatment. Almost all such men see their PSA fall, but most see it rise again within two years. In primary disease, the probe is used during the first prostatectomy to look for nodal spread; there it finds some metastases that PET missed, but it also misses tiny deposits under about 3 mm, so it cannot yet replace the standard extended removal of pelvic lymph nodes.
The same injection also works as a diagnostic scan. A German outpatient centre reported 210 men scanned with it, and a Chinese centre used it for primary diagnosis in 48 men. SPECT is less sensitive than PET, and at low PSA levels it finds clearly fewer recurrences, so the reports present it as an option where PET is not available. Its radiation dose to the patient is small, similar to other technetium-99m scans and lower than gallium-68 or fluorine-18 PET tracers, and the dose to the surgical team is measured in microsieverts per operation.
PSMA I&S is a hospital radiopharmaceutical. It is prepared shortly before use in a licensed radiopharmacy, injected into a vein by nuclear medicine staff, and its radioactivity is mostly gone within a day. It is not a product anyone can buy, mix or take, and nothing about it applies outside that setting.
Mechanism of Action
PSMA I&S binds the enzyme pocket of prostate-specific membrane antigen and is taken into the cell with it. The technetium-99m it carries gives off gamma rays that a SPECT camera can image and a handheld or robotic probe can count.
Binding PSMA
Its glutamate-urea-lysine core fits the active site of PSMA, which prostate cancer cells make in large amounts, and the bound tracer is internalised; blocking with excess unlabelled ligand cut cell binding about 2.6-fold in a 2023 kit study.
Holding technetium
A chain of three D-serines with a mercaptoacetyl group grips technetium-99m. The D-form was chosen over the L-form because it was taken into cells better and stayed intact longer in mice.
Slow clearance, rising contrast
Binding to plasma proteins keeps it in the blood for hours, so tumour-to-background ratios climb overnight; this is why surgery is done about a day after injection.
Gamma detection
Technetium-99m's gamma rays suit SPECT cameras and surgical gamma probes, and with an effective half-life of about four hours in the body little activity remains by the time of surgery the next day.
Published Research
These studies of PSMA I&S were read from their PubMed abstracts on October 30, 2026: the paper that introduced it, the dosimetry and staff-exposure studies, the robot-assisted and open surgery series in recurrent and primary prostate cancer, the diagnostic SPECT series, and the preparation and mouse studies. Several surgical reports name the tracer in the abstract rather than the title; each was read and recorded as a study of this molecule.
Phase 2 trial during first prostatectomy: finds extra nodes, misses too many to skip dissection
In 62 men with localised cancer and more than a 5% risk of nodal spread (NCT04832958), the tracer was injected the day before robot-assisted prostatectomy. No adverse events followed the injection. The probe found nodal disease in two men whose PET had missed it, but its per-patient negative predictive value of 83% was too low to drop the standard lymph node dissection.
TRACE-I: two-year outcomes after robot-assisted salvage surgery
Thirty men with up to three pelvic recurrences on PSMA PET had robot-assisted surgery guided by the tracer. PSA fell in 28 (93%) and reached the target low level in two thirds, but biochemical progression-free survival was 40% at one year and 30% at two; 58% were still free of further treatment at two years.
Guided node removal at first prostatectomy and time to further treatment
In a matched retrospective comparison of 46 men with PET-positive pelvic nodes who had tracer-guided node removal during prostatectomy and 42 who had conventional removal, the guided group went longer before needing further treatment (hazard ratio 0.53). The authors note the small, retrospective design.
SPECT/CT for primary diagnosis in 48 men
Men with suspected prostate cancer were scanned four hours after 0.74 GBq. Against biopsy or surgery the scan was 100% sensitive and 78% specific; higher uptake (SUVmax) went with higher PSA, Gleason score and risk group, and with spread beyond the prostate.
Normal bone uptake compared with two fluorine-18 PET tracers
Across 281 men scanned with PSMA-1007, JK-PSMA-7 or PSMA I&S, normal bone uptake differed between tracers (highest for PSMA-1007) and the parotid gland varied most, making it a poor reference region. The authors judged the technetium SPECT tracer about as useful as the two PET tracers for reading the skeleton.
A new robotic drop-in probe in 13 primary operations
In 13 men having robot-assisted prostatectomy, the probe confirmed the one patient whose SPECT/CT showed suspicious nodes, and there were no complications from the tracer or the dissection. It missed two men with micrometastases smaller than 3 mm, before and during surgery.
What probe count should mark a node as positive
In 30 men from the phase 2 primary-surgery trial, a target-to-background ratio of 2 or more found 72% of involved regions at 88% specificity, and higher cut-offs traded sensitivity for specificity. At a ratio of 2, the probe flagged eight areas PET had not shown, five of which held cancer.
Probe signal tracks PET brightness
In 29 men with recurrent cancer injected the day before surgery, the drop-in probe's counts per second rose with each lesion's SUVmax on PSMA PET (correlation about 0.73 in the body and 0.76 outside it). The link held for lesions with SUVmax of 6 or more but not for fainter ones, which may help choose who suits the operation.
Fifty salvage operations at one centre
In 50 men with recurrence after prostatectomy, every patient had at least one cancer-containing lesion removed. Complications occurred in 26%, 16% of them grade IIIb. Over follow-up, 62% had a further PSA rise and 58% went on to more treatment, so only 42% stayed free of biochemical recurrence.
Phase 2 interim analysis: safe, specific, misses small deposits
The first 12 men in the primary-surgery trial had no adverse events and no intraoperative complications. Per patient, the probe was 67% sensitive and 100% specific; per region, 63% and 99%. The missed disease was micrometastatic.
First prospective test of robot-assisted salvage surgery with the drop-in probe
Twenty men with up to three pelvic recurrences were operated on 19 to 23 hours after injection. Nineteen of 21 PET-visible lesions were removed robotically; per lesion the probe was 86% sensitive and 100% specific. PSA fell by more than half in 12 of 18 men, and 4 of 18 stayed free of recurrence over up to 15 months.
Robot-assisted guidance in 12 high-risk primary cases
After 500 MBq and SPECT/CT, the drop-in probe helped remove PSMA-avid nodes outside the usual template and found 11 metastatic nodes that preoperative gallium-68 PET had not shown. Sensitivity was 76% in the body, with specificity of 69% in the body and 96% outside it; 90% of missed nodes were 3 mm or smaller.
Radiation dosimetry in four healthy volunteers
After a mean of 717 MBq, the effective dose was about 0.0055 mSv per MBq, or roughly 3 to 4.4 mSv in total, comparable to other technetium-99m tracers and lower than gallium-68 and fluorine-18 PET agents. No injection-related adverse events were reported, and ten patients showed high tumour-to-background ratios.
Radiation dose to the staff who make, inject and operate
Measured doses for each person in a single procedure ranged from 0 to 5 microsieverts, highest for the scrub nurse (about 3.2). A scrub nurse doing 100 procedures a year would receive about 0.32 mSv. The dose rate 50 cm from the patient fell from 18.5 microsieverts an hour after injection to 0.56 after surgery.
How much to inject so little activity remains at surgery
German rules allow simplified radiation protection if less than 10 MBq remains in the patient at operation. From dose-rate readings in six patients, the tracer's effective half-life was 4.15 hours, so an injection of 550 MBq about 24 hours before surgery met the limit, and a surgeon could do up to 241 such operations a year under 1 mSv.
Ex vivo uptake separates cancerous from clean lymph nodes
Six men had tracer-guided surgery 24 hours after injection, and 498 removed samples were measured one by one. Cancer-containing samples took up far more tracer than clean nodes (median SUL 3.5 against 0.26); at the best cut-off, sensitivity was 77% and specificity 94%.
Diagnostic SPECT/CT in 210 outpatients
Lesions were found in 65% of men overall. For rising PSA after treatment, detection rose from 20% below 1 ng/mL to 83% above 4 and 100% above 10 ng/mL. The authors say that at low PSA it is clearly worse than PET and should be used only where PET is unavailable.
The paper that introduced it: chemistry, mice and the first patients
A kit gave the tracer at 98% or better purity in more than 50 preparations. In mice it reached PSMA-positive tumours as well as the indium-111 tracer it replaced but cleared more slowly. In patients 94% bound to plasma proteins, lesion contrast kept rising up to 21 hours, and the first tracer-guided operation removed every node seen on PET.
Systematic review of PSMA-targeted surgery
Of 29 reports, all at high or unclear risk of bias, 72% used radioguided surgery and two thirds of those used this tracer. Specificity was consistently higher than sensitivity. Outcome data existed only for its use in salvage surgery, where 22% to 100% of men had a PSA drop over 90% and 50% to 62% later recurred; the method remains investigational.
A cold kit for quick labelling, tested in cells and mice
Labelling a ready-made kit with freshly eluted technetium gave a 92% yield that stayed stable for six hours. About 97% bound to serum proteins; in prostate cancer cells about two thirds of the bound tracer was internalised, and in mice tumour uptake was about 6.5 times that of muscle.
Automated in-house production
Because no approved commercial kit existed, a German group automated the synthesis on a radiochemistry module to good manufacturing practice. Three validation runs gave a yield of about 59% and a radiochemical purity of 93%, with less than 2% free or reduced technetium.
Newer technetium tracers compared with it in mice
Three new N4-PSMA ligands bound PSMA as strongly and reached tumours as well as PSMA I&S in tumour-bearing mice, but bound less to plasma proteins and cleared faster, giving better tumour-to-background ratios. The authors describe PSMA I&S's slow clearance as the limitation they set out to fix.
Dosing Data
PSMA I&S has no approved label anywhere. The rows below are administered activities, the amount of radioactivity injected into a vein, as reported in the human studies carded above. They are measured in megabecquerels (MBq) or gigabecquerels (GBq), not in milligrams, and are chosen by the nuclear medicine department for each procedure.
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 PSMA I&S 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: PSMA I&S 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&S is dosed by radioactivity and labelled with technetium-99m 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 PSMA I&S 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 (Single injection; Dosimetry in healthy volunteers (4 people)).
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: Dosimetry in healthy volunteers (4 people): Imaging up to 24 hours; Robot-assisted surgery, primary high-risk cancer (12 men): SPECT/CT, then surgery; Activity chosen for surgery about 24 hours after injection (6 men measured): One operation.
When effects appear: unknown; no source on this page gives a time to effect for PSMA I&S. 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: No injection-related adverse events in the dosimetry volunteers, the 62-man phase 2 trial or the first 12 men of that trial; Complications of the operation itself: 26% in a 50-man salvage series (16% Clavien-Dindo IIIb) and four grade 3 complications within 30 days in the phase 2 primary-surgery trial; A radiation dose to the patient of about 3 to 4.4 mSv per injection, similar to other technetium-99m scans; Small radiation doses to staff, up to about 5 microsieverts per person per procedure. Full list and cautions ↓
When to stop or get help: unknown; no label or trial on file sets rules for stopping PSMA I&S. 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 PSMA I&S (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 PSMA I&S 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 PSMA I&S's expected mass, 1,299.4 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: Drugs@FDA and the EMA medicines list hold no record (searched October 28, 2026)). 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. The tracer itself has caused no reported adverse events; the risks come from the surgery it guides and from radiation.
Contraindications & Cautions
There is no approved label, so there are no official contraindications. Points from the studies above:
Legal Status
PSMA I&S is not approved by any regulator checked. Hospitals prepare it under trial or national pharmacy rules.
Frequently Asked Questions
?What is PSMA I&S?
A small molecule that binds prostate-specific membrane antigen, labelled with radioactive technetium-99m. 'I&S' stands for imaging and surgery: it is used for SPECT scans and to let a surgeon's gamma probe find prostate cancer in lymph nodes.
?Is it approved?
No. Drugs@FDA and the EMA list hold no record. Hospitals make it in their own radiopharmacies for trials and local use.
?Why is it injected the day before surgery?
It clears slowly from the blood because most of it binds to plasma proteins, while it keeps collecting in the cancer, so the contrast between tumour and background is best after about a day.
?Does PSMA-guided surgery cure recurrent prostate cancer?
Usually not on its own. In the studies above PSA fell in almost every man, but most had a further rise within two years; some went longer before needing other treatment.
?Can it replace removing the pelvic lymph nodes at prostatectomy?
Not yet. In the primary-surgery trials it found some nodes that PET missed but also missed small deposits, so the standard dissection was still needed.
?How does it compare with a PSMA PET scan?
SPECT with this tracer is cheaper and more widely available but less sensitive, especially when PSA is low. The reports suggest it where PET is not available.
?Is it a peptide people can buy?
No. It is a short-lived radioactive drug prepared and injected in hospitals.
References
- [other] PubChem CID 165413018, PSMA I&S: formula C59H82N10O21S, molecular weight 1299.4. Read October 28, 2026. https://pubchem.ncbi.nlm.nih.gov/compound/165413018
- [registry] ClinicalTrials.gov API v2, read October 28, 2026: NCT04832958 (phase 2, imaging-guided surgery for lymph node metastases, completed); NCT04857502 (early phase 1, biodistribution, recruiting).
- [pubmed] Quarta L, et al. "PSMA Radio-guided Surgery to Identify Lymph Node Metastases in Prostate Cancer Patients Undergoing Robot-assisted Radical Prostatectomy and Extended Pelvic Lymph Node Dissection: Results of a Phase 2 Prospective Study." Eur Urol, 2026. PMID: 42580956.
- [pubmed] Zuur LG, et al. "Oncological Outcomes of Robot-assisted PSMA-guided Salvage Surgery in Recurrent Prostate Cancer: Insights from the Prospective TRACE-I Trial." Eur Urol Focus, 2026. PMID: 42668258.
- [pubmed] Korn P, et al. "Radical Prostatectomy Combined with Prostate Specific Membrane Antigen-radioguided Lymph Node Dissection is Associated with Longer Treatment-free Survival for Patients with Primary Lymph Node-positive Prostate Cancer." Eur Urol Open Sci, 2025;82:201-207. PMID: 41322961.
- [pubmed] Li M, et al. "[(99)ᵐTc]Tc-PSMA-I&S SPECT/CT quantitative parameters for risk stratification and metastasis prediction in primary prostate cancer: a retrospective study." Front Med (Lausanne), 2025;12:1654685. PMID: 41098985.
- [pubmed] Mikó ZS, et al. "Different PSMA Radiopharmaceuticals: A Comparative Study of [(18)F]F-PSMA-1007, [(18)F]F-JK-PSMA-7, and [(99m)Tc]Tc-PSMA-I&S in the Skeletal System." Pharmaceuticals (Basel), 2024;17(11). PMID: 39598371.
- [pubmed] Harke NN, et al. "Feasibility of Using a Novel Drop-In Gamma Probe for 99m Tc-PSMA-I&S-Guided Lymph Node Detection During Robot-Assisted Radical Prostatectomy for Primary Prostate Cancer." Clin Nucl Med, 2024;49(10):948-952. PMID: 38968541.
- [pubmed] Quarta L, et al. "Defining the optimal target-to-background ratio to identify positive lymph nodes in prostate cancer patients undergoing robot-assisted [(99m)Tc]Tc-PSMA radioguided surgery: updated results and ad interim analyses of a prospective phase II study." Eur J Nucl Med Mol Imaging, 2024;51(12):3789-3798. PMID: 38861182.
- [pubmed] Berrens AC, et al. "Strong Correlation Between SUV(max) on PSMA PET/CT and Numeric Drop-In γ-Probe Signal for Intraoperative Identification of Prostate Cancer Lesions." J Nucl Med, 2024;65(4):548-554. PMID: 38485277.
- [pubmed] Mayr R, et al. "Prostate-specific membrane antigen-radioguided surgery salvage lymph node dissection: experience with fifty oligorecurrent prostate cancer patients." World J Urol, 2024;42(1):483. PMID: 39133316.
- [pubmed] Gandaglia G, et al. "Prostate-specific membrane antigen Radioguided Surgery to Detect Nodal Metastases in Primary Prostate Cancer Patients Undergoing Robot-assisted Radical Prostatectomy and Extended Pelvic Lymph Node Dissection: Results of a Planned Interim Analysis of a Prospective Phase 2 Study." Eur Urol, 2022;82(4):411-418. PMID: 35879127.
- [pubmed] de Barros HA, et al. "Robot-assisted Prostate-specific Membrane Antigen-radioguided Salvage Surgery in Recurrent Prostate Cancer Using a DROP-IN Gamma Probe: The First Prospective Feasibility Study." Eur Urol, 2022;82(1):97-105. PMID: 35339318.
- [pubmed] Gondoputro W, et al. "Robot-Assisted Prostate-Specific Membrane Antigen-Radioguided Surgery in Primary Diagnosed Prostate Cancer." J Nucl Med, 2022;63(11):1659-1664. PMID: 35241483.
- [pubmed] Urbán S, et al. "Radiation Dosimetry of (99m)Tc-PSMA I&S: A Single-Center Prospective Study." J Nucl Med, 2021;62(8):1075-1081. PMID: 33277398.
- [pubmed] Aalbersberg EA, et al. "Occupational Radiation Exposure of Radiopharmacy, Nuclear Medicine, and Surgical Personnel During Use of [(99m)Tc]Tc-PSMA-I&S for Prostate Cancer Surgery." J Nucl Med Technol, 2021;49(4):334-338. PMID: 34330802.
- [pubmed] Schmidt D, et al. "Dose estimates of occupational radiation exposure during radioguided surgery of Tc-99m-PSMA-labeled lymph nodes in recurrent prostate cancer." Nuklearmedizin, 2021;60(6):425-433. PMID: 34768300.
- [pubmed] Mix M, et al. "(99m)Tc-labelled PSMA ligand for radio-guided surgery in nodal metastatic prostate cancer: proof of principle." EJNMMI Res, 2021;11(1):22. PMID: 33661414.
- [pubmed] Werner P, et al. "[(99cm)Tc]Tc-PSMA-I&S-SPECT/CT: experience in prostate cancer imaging in an outpatient center." EJNMMI Res, 2020;10(1):45. PMID: 32382945.
- [pubmed] Robu S, et al. "Preclinical Evaluation and First Patient Application of 99mTc-PSMA-I&S for SPECT Imaging and Radioguided Surgery in Prostate Cancer." J Nucl Med, 2017;58(2):235-242. PMID: 27635024.
- [pubmed] Berrens AC, et al. "State of the Art in Prostate-specific Membrane Antigen-targeted Surgery-A Systematic Review." Eur Urol Open Sci, 2023;54:43-55. PMID: 37361200.
- [pubmed] Fuscaldi LL, et al. "Radiochemical and biological assessments of a PSMA-I&S cold kit for fast and inexpensive (99m)Tc-labeling for SPECT imaging and radioguided surgery in prostate cancer." Front Chem, 2023;11:1271176. PMID: 37901160.
- [pubmed] Plhak E, et al. "Development of in-House Synthesis and Quality Control of [(99m)Tc]Tc-PSMA-I&S." Molecules, 2023;28(2). PMID: 36677636.
- [pubmed] Kunert JP, et al. "Synthesis and preclinical evaluation of novel (99m)Tc-labeled PSMA ligands for radioguided surgery of prostate cancer." EJNMMI Res, 2023;13(1):2. PMID: 36645586.
Sources & Citations
Every study on this page was read from its PubMed record on October 30, 2026. Approval status comes from Drugs@FDA (openFDA) and the EMA medicines list, and trial status from the ClinicalTrials.gov API, read October 28, 2026. The formula is 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. Talk to a licensed clinician about your own situation.