Trofolastat
A PSMA-seeking molecule for gamma-camera scans of prostate cancer
Trofolastat, known in most papers as 99mTc-MIP-1404, is a small molecule built on the glutamate-urea motif that binds prostate-specific membrane antigen (PSMA), with a chelator holding technetium-99m. That label works on the SPECT gamma cameras found in most hospitals, so it offers PSMA imaging where PET is not available. It is a peptidomimetic rather than a true peptide. Studies in hundreds of men, mostly in Europe, have used it; it is not approved.
Used in human trials: 710 ± 64 MBq, Single injection, Intravenous (Technetium-99m trofolastat SPECT/CT, recurrence (225 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?
PSMA is an enzyme on the surface of most prostate cancer cells, and small molecules that inhibit it have become the basis of both imaging and treatment, from gallium-68 and fluorine-18 PET tracers to lutetium-177 therapy. Most of those need PET scanners. Trofolastat was developed by Molecular Insight Pharmaceuticals and then Progenics to carry technetium-99m, the most widely used isotope in nuclear medicine, for SPECT gamma cameras.
In laboratory tests it bound PSMA tightly and specifically, and among four candidates it had the best balance of tumour uptake and fast clearance from kidneys and other organs. The first human study, in healthy men and men with metastatic prostate cancer, showed rapid blood clearance, uptake in salivary and lacrimal glands, and only about 7% of activity in urine, which keeps the bladder from hiding nearby disease. Lesions in bone and lymph nodes showed within an hour, and it found more lesions than a bone scan.
A European phase 2 study in 105 men with intermediate- or high-risk cancer, scanned before prostatectomy and extended lymph-node dissection, detected the cancer in the gland in 94%, and uptake correlated with Gleason grade. For lymph nodes, sensitivity was 50% and specificity 87% on visual reading. A phase 3 study in men with low-grade cancer is listed as completed in 2017, but its results were not found in PubMed.
Most later evidence comes from German, Swedish and British academic centres using it in routine care. In 225 men with biochemical recurrence, lesions were found in 77%, rising to 90% when PSA was 2 ng/mL or above; findings changed treatment plans in most documented cases. In a Swedish phase 2 comparison with gallium-68 PSMA-11 PET, it was less sensitive lesion by lesion but led to the same treatment decision in 91% of men. It has also been used to select men for lutetium-177 PSMA therapy, where higher liver uptake means the PET cut-off cannot be copied directly, and to guide surgeons to positive lymph nodes with a hand-held probe.
PSMA PET is more sensitive where it is available, and trofolastat's role is mainly where it is not. It has no FDA or EMA approval and is prepared from a kit in hospital radiopharmacies.
Mechanism of Action
Trofolastat is an imaging agent. It binds PSMA and carries technetium-99m for a gamma camera; it does not treat cancer.
PSMA binding
Binds PSMA with a dissociation constant of about 1 nM and is taken into the cell (2013 study).
Technetium-99m SPECT
Imaged 3-4 hours after injection on standard gamma cameras (2018 studies).
Low urinary activity
About 7% in urine, so the bladder interferes less with pelvic imaging (2014 study).
Normal uptake
Salivary and lacrimal glands, kidneys and liver, with liver higher than gallium-68 PSMA-11 (2014 and 2023 studies).
Published Research
These studies were read from their PubMed abstracts on October 29, 2026: thirteen in men with prostate cancer or healthy volunteers, and one laboratory and mouse study. Two are titled for '[99mTc]Tc-PSMA' and carded because their abstracts name MIP-1404 as the tracer.
First in humans: healthy men and metastatic cancer
Six healthy men and six with metastatic cancer received MIP-1404 and a sister compound in crossover. Both cleared blood quickly; MIP-1404 had only 7% urinary activity against 26%. Bone and node lesions showed within an hour with 3:1 to 9:1 contrast, and more lesions than on bone scans.
Phase 2: 105 men before prostatectomy
Cancer was detected in 98 of 105 men (94%) with acceptable reader agreement. Visual scores and tumour-to-background ratios tracked Gleason grade. Lymph-node involvement was found with 50% sensitivity and 87% specificity; the ratio predicted node spread with 90% sensitivity.
First experience in recurrence
Sixty men with rising PSA after treatment received about 733 MBq. Lesions were found in 70%: 91.4% when PSA was above 2 ng/mL and 40% below. Lesions included nodes, local recurrence and bone.
225 men with biochemical recurrence
After 710 ± 64 MBq, positive lesions were seen in 77%: nodes in 47%, bone in 27%, local recurrence in 25%. Detection was 90% at PSA ≥2 ng/mL and 54% below. A tumour board changed treatment for 74% of those with follow-up.
Primary staging in 93 men
Uptake in the prostate was seen in 97% of men with untreated cancer, with 97-99% agreement between readers. Total prostate uptake was higher with Gleason 8 or more and PSA of 10 or more, and predicted spread with 82% sensitivity and 76% specificity.
Low and very low PSA
In 50 men with recurrence and PSA under 1 ng/mL, lesions were found in 44% at PSA 0.2-0.5 and 56% at 0.5-1. Gleason 8 or more and androgen deprivation predicted a positive scan, and the result changed therapy in half.
Treatment response pilot
In 28 men scanned before and after hormone therapy, docetaxel or radiotherapy, change in uptake agreed with PSA response in 75%, better than CT, which agreed in 50-57%.
Whole-body tumour burden
In 125 men with recurrence, whole-body PSMA tumour volume and total lesion uptake correlated with PSA. In 50 scanned before and after treatment, total uptake agreed with PSA response in 80%, CT in 52-60%.
Reader agreement over time
Three readers judged 96 lesions in 22 men on scans about 10 months apart. Quantitative SPECT gave 90.6% agreement against 76% for visual SPECT and 56.3% for planar images.
Choosing men for lutetium-177 PSMA therapy
Compared with matched men scanned with gallium-68 PSMA-11, lesion uptake was similar but liver uptake higher, so lesion-to-liver ratios were lower (2.7 vs 3.5). The authors advise a lower cut-off if used to select patients.
Companion scan before lutetium-177 PSMA
In 46 men with castration-resistant disease, image quality was excellent in 98% and findings matched post-therapy lutetium scans almost perfectly. Uptake above liver predicted response and longer progression-free survival, though 27% of responders did not show it.
Radioguided lymph-node surgery
Nine men with recurrence seen on PSMA PET received a median 747 MBq the day before surgery. SPECT showed 9 of 17 lesions, but the probe found all but two during surgery plus two extra metastases; PSA fell in six.
Phase 2 vs gallium-68 PSMA-11 PET
In newly diagnosed high-risk cancer, patient-level sensitivity against PSMA PET was 81% for nodes and 85% for bone, with no false positives. PSMA PET found more lesions, but treatment decisions agreed in 30 of 33 men.
Which recurrent patients benefit
In 143 men given about 664 MBq, detection rose with PSA and grade: for ISUP grade 4-5 it was 29% at PSA ≤0.2 and 75-100% above that. The authors suggest using it at PSA >0.2 for high grade, >0.5 for lower grade.
Selecting men for primary staging
In 91 men given a median 670 MBq, PSA level and ISUP grade both predicted metastases. Detection reached 50% at PSA >20 with grade 4-5 or PSA >50 with grade 1-3, and metastases were found in everyone with PSA >50.
Choosing MIP-1404 among four candidates
All four technetium-99m PSMA inhibitors bound PSMA at about 1-4 nM and were blocked by another inhibitor. In mice, MIP-1404 combined high tumour uptake with rapid clearance from kidneys and other organs and showed no uptake in PSMA-negative tumours.
Dosing Data
Trofolastat has no approved label. It is dosed by radioactivity for a single scan; rows are from the carded human studies.
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 Trofolastat 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: Trofolastat 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: “Trofolastat is labelled from a kit in a hospital radiopharmacy and dosed by radioactivity; 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 Trofolastat 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; Technetium-99m trofolastat SPECT/CT, recurrence (225 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: Technetium-99m trofolastat SPECT/CT, recurrence (225 men): Imaging 3-4 hours later; Technetium-99m trofolastat, radioguided surgery: SPECT about 17 hours, surgery about 22 hours later.
When effects appear: unknown; no source on this page gives a time to effect for Trofolastat. 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: The abstracts read report no safety problems; the first human study described rapid clearance and good imaging; Expected normal uptake in salivary and lacrimal glands, kidneys and liver. Full list and cautions ↓
When to stop or get help: unknown; no label or trial on file sets rules for stopping Trofolastat. Treat a severe or unexpected reaction as a reason to stop and see a doctor.
Source: the Side Effects section below (“From the human studies above”).
Interactions
Unknown: a PubMed search for human interaction studies of Trofolastat (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 Trofolastat 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 Trofolastat's expected mass, 954.8 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 human studies above.
Contraindications & Cautions
No approved label exists, so there are no official contraindications. Points from the studies:
Legal Status
Trofolastat is investigational in every jurisdiction checked.
Frequently Asked Questions
?What is trofolastat?
A technetium-99m labelled PSMA inhibitor for SPECT/CT scans of prostate cancer, usually called 99mTc-MIP-1404.
?How does it compare with PSMA PET?
It finds fewer small lesions, but in one study treatment decisions matched PSMA PET in 91% of men. It runs on more widely available gamma cameras.
?Is it a peptide?
It is a small peptidomimetic built on glutamate and urea, grouped with PSMA ligands such as piflufolastat.
?Is it approved?
No.
References
- [other] PubChem CID 46241486 (synonyms trofolastat [USAN], MIP-1404): formula C37H50N10O20, molecular weight 954.8. Read October 28, 2026. https://pubchem.ncbi.nlm.nih.gov/compound/46241486
- [registry] ClinicalTrials.gov API v2, read October 28, 2026: NCT02615067 (phase 3, men with biopsy-proven low-grade prostate cancer, completed).
- [clinical-trial] Vallabhajosula S, et al. "99mTc-labeled small-molecule inhibitors of prostate-specific membrane antigen: pharmacokinetics and biodistribution studies in healthy subjects and patients with metastatic prostate cancer." J Nucl Med, 2014;55(11):1791-8. PMID: 25342385.
- [clinical-trial] Goffin KE, et al. "Phase 2 Study of (99m)Tc-Trofolastat SPECT/CT to Identify and Localize Prostate Cancer in Intermediate- and High-Risk Patients Undergoing Radical Prostatectomy and Extended Pelvic LN Dissection." J Nucl Med, 2017;58(9):1408-1413. PMID: 28302763.
- [pubmed] Reinfelder J, et al. "First Experience With SPECT/CT Using a 99mTc-Labeled Inhibitor for Prostate-Specific Membrane Antigen in Patients With Biochemical Recurrence of Prostate Cancer." Clin Nucl Med, 2017;42(1):26-33. PMID: 27775936.
- [pubmed] Schmidkonz C, et al. "(99m) Tc-MIP-1404-SPECT/CT for the detection of PSMA-positive lesions in 225 patients with biochemical recurrence of prostate cancer." Prostate, 2018;78(1):54-63. PMID: 29105797.
- [pubmed] Schmidkonz C, et al. "SPECT/CT With the PSMA Ligand 99mTc-MIP-1404 for Whole-Body Primary Staging of Patients With Prostate Cancer." Clin Nucl Med, 2018;43(4):225-231. PMID: 29401151.
- [pubmed] Schmidkonz C, et al. "PSMA SPECT/CT with (99m)Tc-MIP-1404 in biochemical recurrence of prostate cancer: predictive factors and efficacy for the detection of PSMA-positive lesions at low and very-low PSA levels." Ann Nucl Med, 2019;33(12):891-898. PMID: 31502084.
- [pubmed] Schmidkonz C, et al. "Assessment of Treatment Response by 99mTc-MIP-1404 SPECT/CT: A Pilot Study in Patients With Metastatic Prostate Cancer." Clin Nucl Med, 2018;43(8):e250-e258. PMID: 29916921.
- [pubmed] Schmidkonz C, et al. "99mTc-MIP-1404 SPECT/CT for Assessment of Whole-Body Tumor Burden and Treatment Response in Patients With Biochemical Recurrence of Prostate Cancer." Clin Nucl Med, 2020;45(8):e349-e357. PMID: 32558706.
- [pubmed] Schmidkonz C, et al. "99mTc-MIP-1404 SPECT/CT for Patients With Metastatic Prostate Cancer: Interobserver and Intraobserver Variability in Treatment-Related Longitudinal Tracer Uptake Assessments of Prostate-Specific Membrane Antigen-Positive Lesions." Clin Nucl Med, 2020;45(2):105-112. PMID: 31876822.
- [pubmed] Cook GJR, et al. "Eligibility for (177)Lu-PSMA Therapy Depends on the Choice of Companion Diagnostic Tracer: A Comparison of (68)Ga-PSMA-11 and (99m)Tc-MIP-1404 in Metastatic Castration-Resistant Prostate Cancer." J Nucl Med, 2023;64(2):227-231. PMID: 36302657.
- [pubmed] Derlin T, et al. "(99m)Tc-MIP-1404 SPECT/CT Companion Diagnostic for (177)Lu-PSMA Therapy in Metastatic Castration-Resistant Prostate Cancer." J Nucl Med, 2025;66(3):366-372. PMID: 39915124.
- [pubmed] Koehler D, et al. "Feasibility of (99m)Tc-MIP-1404 for SPECT/CT Imaging and Subsequent PSMA-Radioguided Surgery in Early Biochemically Recurrent Prostate Cancer: A Case Series of 9 Patients." J Nucl Med, 2023;64(1):59-62. PMID: 35835582.
- [pubmed] Saudi A, et al. "Head-to-head comparison of (99m)Tc-MIP-1404 CZT SPECT/CT and (68)Ga/PSMA-11 PET/CT for primary staging of high-risk prostate cancer: a phase II study." EJNMMI Res, 2026;16(1). PMID: 42489957.
- [pubmed] Liepe K, et al. "The diagnostic accuracy of [99mTc]Tc-PSMA SPECT/CT for recurrent prostate cancer based on individual patient attributes." Eur J Nucl Med Mol Imaging, 2026;53(4):2245-2256. PMID: 41174097.
- [pubmed] Liepe K, et al. "Patient selection for primary staging with [99mTc]Tc-PSMA SPECT/CT: influence of combined PSA and ISUP grade on detection of metastatic disease." Eur J Nucl Med Mol Imaging, 2026. PMID: 42711500.
- [pubmed] Hillier SM, et al. "99mTc-labeled small-molecule inhibitors of prostate-specific membrane antigen for molecular imaging of prostate cancer." J Nucl Med, 2013;54(8):1369-76. PMID: 23733925.
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 (October 29, 2026). 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.