Technetium Tc 99m Etarfolatide
A folic acid tracer that shows folate receptors on tumours and inflamed joints, built to pick patients for vintafolide
Many ovarian, lung and other cancers carry a receptor that grabs folic acid, and so do activated immune cells in inflamed joints. Etarfolatide is folic acid joined to a small peptide that holds radioactive technetium-99m, so a SPECT scan shows where those receptors are. It was developed alongside vintafolide, a folate-guided cancer drug, to find the patients most likely to respond. The pairing faltered in phase 3; the EU application was withdrawn in 2014 and the US never approved it.
Used in human trials: About 740 MBq (±20%) of technetium-99m etarfolatide, Single injection, 1 to 3 minutes after intravenous folic acid, Intravenous (Study: phase 1, six healthy 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?
Cells take in folic acid, a B vitamin, partly through a receptor on their surface. The alpha form of this folate receptor is plentiful on many epithelial cancers, including most ovarian cancers and many lung, endometrial and breast cancers, while the beta form appears on macrophages, immune cells, once they are activated by inflammation. A drug or tracer with folic acid attached can ride that receptor into those cells.
Etarfolatide, developed under the code EC20, is folic acid linked to a short peptide chain that grips technetium-99m, a radioactive isotope that ordinary gamma cameras can image. Injected into a vein, it reaches receptor-carrying tissue within an hour or two and shows up on an ordinary gamma camera with SPECT. In mice it cleared from the blood in minutes and was excreted unchanged in the urine; the kidneys, which carry the receptor themselves, were the main other organ to take it up. A small dose of plain folic acid given just before the scan sharpens the contrast.
Its main job was as a companion test for vintafolide, a folate-guided chemotherapy that attaches a vinca alkaloid to folic acid. The idea was simple: if a patient's tumours do not take up the tracer, the drug has nothing to grab. In the randomised phase 2 PRECEDENT trial in platinum-resistant ovarian cancer, adding vintafolide to standard chemotherapy helped most in women whose every lesion was positive on the scan, and not at all in women with no positive lesions. A single-arm trial found the same gradient for disease control and survival.
That made etarfolatide a companion diagnostic: a scan meant to decide who gets a targeted drug. But the pairing did not hold up: a 2015 review records that the promising phase 2 results were not confirmed in phase 3, the phase 3 PROCEED trial is listed as terminated, and the European marketing application for etarfolatide, as Folcepri, was withdrawn in May 2014. It has never been approved in the US.
The agent also found a second use because of the beta receptor on macrophages. In rats with arthritis it collected in inflamed limbs and disappeared when macrophages were removed. In 40 people with rheumatoid arthritis it showed more active joints than a doctor's examination found, and in 25 people with knee osteoarthritis it showed activated macrophages in three quarters of knees, in amounts that tracked pain and X-ray damage. The osteoarthritis authors called it the first direct evidence in living people that macrophages take part in the disease. It did not become an approved test.
Safety in the published studies has been unremarkable: the 2008 pilot of 154 patients called it well tolerated, and a phase 1 study in six healthy Japanese men saw only mild events. The radiation dose was judged comparable to existing diagnostic agents.
Mechanism of Action
Etarfolatide carries technetium-99m to cells that display the folate receptor, the alpha form on many cancers and the beta form on activated macrophages, so a SPECT scan can map them.
Folate receptor alpha
Plentiful on most epithelial ovarian cancers and many lung, endometrial and breast cancers; the scan was used to predict who would respond to vintafolide.
Folate receptor beta
Appears on macrophages once they are activated; this is how the tracer shows inflamed joints in arthritis, and why depleting macrophages in rats abolished uptake.
Folic acid first
Free folic acid competes for the receptor; a small dose just before the scan improved tumour-to-background contrast in mice and was given in the phase 1 study.
Kidney clearance
The tracer leaves mainly in the urine; the kidneys carry the receptor and are the main non-target organ, and pemetrexed cut kidney uptake in mice.
Published Research
Studies of etarfolatide, also titled 99mTc-EC20 or FolateScan, read from their PubMed abstracts on October 29, 2026. The human studies come first: the cancer pilot, the vintafolide trials in which the scan sorted patients, the phase 1 study and the arthritis studies; then three reviews and the animal work. Six cards are studies whose titles name only the trial drug or the condition; their abstracts name etarfolatide as the agent used.
154 patients with solid tumours
In a pilot of 154 patients with tumours of at least 1.5 cm, most of them kidney cancer, 68% showed tumour uptake on whole-body and SPECT images 1 to 2 hours after injection, and 67% had folate receptor alpha on tissue staining. Agreement between the two was poor (61%), which the authors put down partly to biopsies taken at a different time and to the stain missing the beta form of the receptor. The agent was well tolerated.
Active joints in rheumatoid arthritis
Forty people with rheumatoid arthritis, plus patients with osteoarthritis or other inflammatory conditions and 5 healthy subjects, received 0.1 mg of EC20 labelled with 20 to 25 mCi of technetium-99m (marketed for study as FolateScan). Scans showed more involved joints than the physical examination in about two thirds of patients, and the count of involved joints correlated with two blood markers of inflammation, the sedimentation rate and C-reactive protein. Uptake was also seen in osteoarthritic joints.
Picking lung-cancer patients for vintafolide
In a multicentre trial of the folate-drug conjugate vintafolide (EC145) in advanced lung adenocarcinoma, only patients with EC20 uptake in at least one lesion were enrolled (43 of 60 screened). Patients whose every target lesion took up EC20 tended to do better than those with mixed uptake (clinical benefit 50% against 14%; survival 47 against 15 weeks), but neither difference was significant.
PRECEDENT: randomised phase 2
In 149 women with platinum-resistant ovarian cancer, adding vintafolide to pegylated liposomal doxorubicin lengthened median progression-free survival from 2.7 to 5.0 months. Optional etarfolatide scans sorted patients: with every lesion receptor-positive, progression-free survival was 5.5 months against 1.5 on doxorubicin alone; patients with no positive lesions got no benefit. The authors conclude etarfolatide can identify who is likely to benefit.
Lesion uptake and response
In a single-arm phase 2 trial, 43 women with advanced ovarian or endometrial cancer were scanned before vintafolide. Of 139 evaluable lesions, 110 were positive; disease was controlled in 56% of positive lesions against 21% of negative ones. Median overall survival was 14.6, 9.6 and 3.0 months in patients with all, some or no lesions positive.
Phase 1 in healthy Japanese men
Six healthy men received intravenous folic acid and, one to three minutes later, about 740 MBq of technetium-99m etarfolatide. Five mild, non-serious adverse events occurred in three men, three judged related to the agents. Blood activity fell rapidly in two phases, the kidneys cleared most of it, and nothing was retained after 24 hours; the estimated radiation dose at 925 MBq was no higher than that of current diagnostic agents.
Side effects by receptor status
An exploratory PRECEDENT analysis of 94 patients sorted by etarfolatide scan (38 all lesions positive, 36 some, 20 none) found that receptor status did not change the side-effect profile of vintafolide plus doxorubicin or doxorubicin alone, and severe drug-related events were uncommon in every group.
Activated macrophages in osteoarthritis
Twenty-five people with knee osteoarthritis had SPECT-CT of both knees and whole-body imaging. The tracer, which binds folate receptor beta on activated (not resting) macrophages, showed them in 76% of knees; the amount correlated with knee pain and with joint-space narrowing and bone spurs on X-ray, and painful finger, wrist, ankle and toe joints were more likely to show uptake.
Properties and clinical use
A review of imaging the folate receptor with technetium-99m etarfolatide: the receptor appears on ovarian, non-small cell lung, endometrial and breast cancers, tissue sampling is invasive and limited, and the agent, then in late-phase trials in Europe and the US, images the receptor across the whole body to guide targeted drugs such as vintafolide and farletuzumab.
Vintafolide and its companion scan
A review of folate-targeted treatment of platinum-resistant ovarian cancer: folate receptor alpha is on almost all epithelial ovarian cancers, vintafolide had reached phase 3, and etarfolatide was described as a non-invasive way to select the patients who might benefit.
Phase 3 did not confirm phase 2
A 2015 review of folate-receptor targeting in cancer, covering the antibody farletuzumab and the vintafolide-plus-etarfolatide pairing. Its summary: the promising phase 2 results had not been confirmed in phase 3, and better patient selection and new combinations were needed.
Synthesis and first mouse data
EC20, a folate-peptide chelator designed to hold technetium-99m, bound receptor-positive tumour cells with high affinity (about 3 nM). In mice it left the blood with a half-life of about 4 minutes, was excreted unchanged in urine, and collected mainly in receptor-positive tumours and the kidneys.
Arthritic rats light up
In rats with adjuvant-induced arthritis, EC20 gathered in the inflamed limbs but not in healthy rats' limbs; excess free folic acid blocked it, and depleting macrophages removed both the receptor and the uptake, showing the signal came from activated macrophages.
Preclinical tumour imaging
In mice, tumour uptake was specific and rose with the tumour's receptor level and size, did not depend on where the tumour sat or how the agent was injected, and a version built from D-amino acids took up less. Co-injecting one equivalent of free folic acid raised tumour-to-normal-tissue ratios up to 2.7-fold, the basis for giving folic acid before scans.
Protecting the kidneys with pemetrexed
In tumour-bearing mice, giving the antifolate pemetrexed an hour before the tracer cut kidney uptake by roughly two thirds to three quarters without lowering tumour uptake, while the antifolate CB3717 lowered both. The receptor-rich kidneys are the main non-target organ for radiofolates.
Dosing Data
Etarfolatide has no approved label. These are the amounts given in published human studies, as a single injection of a radioactive tracer before SPECT.
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 Technetium Tc 99m Etarfolatide 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: Technetium Tc 99m Etarfolatide 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: “Etarfolatide is dosed by radioactivity and labelled with technetium-99m in a radiopharmacy shortly before the scan, so there is nothing to calculate.”
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 Technetium Tc 99m Etarfolatide 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, 1 to 3 minutes after intravenous folic acid; Study: phase 1, six healthy 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: Study: phase 1, six healthy men: Imaging and sampling up to 24 hours; Study: rheumatoid arthritis and other conditions, 63 participants: Imaging of joints and other target tissues.
When effects appear: unknown; no source on this page gives a time to effect for Technetium Tc 99m Etarfolatide. 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: Well tolerated in the 154-patient cancer pilot (PMID 18483093); Five mild, non-serious events in three of six healthy men, three judged related to folic acid or the tracer (PMID 26238440); Radiation dose judged no higher than current diagnostic agents at 925 MBq (PMID 26238440). Full list and cautions ↓
When to stop or get help: unknown; no label or trial on file sets rules for stopping Technetium Tc 99m Etarfolatide. 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 Technetium Tc 99m Etarfolatide (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 Technetium Tc 99m Etarfolatide 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 Technetium Tc 99m Etarfolatide's expected mass, 745.7 Da, from this entry's molecular data. Trust & Verification explains what independent testing can and cannot show.
Legal status
US: Discontinued (Never approved). 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
Etarfolatide was never approved; its EU application was withdrawn.
Frequently Asked Questions
?What is etarfolatide?
Folic acid joined to a short peptide that holds technetium-99m. It binds folate receptors, so a SPECT scan shows tumours and activated immune cells that carry them. Its development code was EC20.
?What was it for?
Mainly to choose patients for vintafolide, a folate-guided cancer drug: in ovarian cancer trials, patients whose lesions all took up the tracer did best on the drug. It was also tested for showing inflamed joints in arthritis.
?Why was it not approved?
Its partner drug did not confirm its phase 2 benefit in phase 3, the phase 3 trial was terminated, and the EU application for etarfolatide, as Folcepri, was withdrawn in May 2014. No US application is on record.
?Why give folic acid before the scan?
A small dose of free folic acid improved the contrast between tumour and normal tissue in mice and was part of the human protocols. Free folic acid competes for the same receptor, so the timing is fixed by the protocol.
?Is it safe?
In the published studies it was well tolerated, with only mild events in a phase 1 study of six men. It is a radioactive tracer given once, in a nuclear medicine department.
References
- [other] PubChem CID 135428923, Etarfolatide (synonyms Folcepri, EC-20): formula C29H35N11O11S, molecular weight 745.7. Read October 28, 2026. https://pubchem.ncbi.nlm.nih.gov/compound/135428923
- [other] European Medicines Agency, medicines list (JSON report, downloaded October 28, 2026): Folcepri (etarfolatide): orphan medicine, marketing application withdrawn, withdrawal date May 16, 2014; for SPECT imaging.
- [other] US FDA, Drugs@FDA (openFDA): no application for etarfolatide. Read October 28, 2026.
- [other] ClinicalTrials.gov API v2, searches 'etarfolatide' and 'EC20', read October 29, 2026: NCT01748864 (phase 1, 99mTc-etarfolatide in normal volunteers, completed); FolateScan (technetium Tc 99m EC20) studies NCT01689636, NCT01686256, NCT01689714, NCT01684098, NCT01689662, NCT01689766, NCT01689727, NCT00588393 and NCT01237405, all completed; the vintafolide trials NCT00507741 and NCT00722592 (phase 2, completed) and NCT01170650 (phase 3 PROCEED, terminated). https://clinicaltrials.gov/search?term=etarfolatide
- [clinical-trial] Fisher RE, et al. "Exploratory study of 99mTc-EC20 imaging for identifying patients with folate receptor-positive solid tumors." J Nucl Med, 2008;49(6):899-906. PMID: 18483093.
- [clinical-trial] Matteson EL, et al. "Assessment of disease activity in rheumatoid arthritis using a novel folate targeted radiopharmaceutical Folatescan." Clin Exp Rheumatol, 2009;27(2):253-9. PMID: 19473565.
- [clinical-trial] Edelman MJ, et al. "Multicenter trial of EC145 in advanced, folate-receptor positive adenocarcinoma of the lung." J Thorac Oncol, 2012;7(10):1618-21. PMID: 22982661.
- [clinical-trial] Naumann RW, et al. "PRECEDENT: a randomized phase II trial comparing vintafolide (EC145) and pegylated liposomal doxorubicin (PLD) in combination versus PLD alone in patients with platinum-resistant ovarian cancer." J Clin Oncol, 2013;31(35):4400-6. PMID: 24127448.
- [clinical-trial] Morris RT, et al. "Phase II study of treatment of advanced ovarian cancer with folate-receptor-targeted therapeutic (vintafolide) and companion SPECT-based imaging agent (99mTc-etarfolatide)." Ann Oncol, 2014;25(4):852-858. PMID: 24667717.
- [clinical-trial] Yamada Y, et al. "Phase I clinical trial of 99mTc-etarfolatide, an imaging agent for folate receptor in healthy Japanese adults." Ann Nucl Med, 2015;29(9):792-8. PMID: 26238440.
- [clinical-trial] Herzog TJ, et al. "Adverse Event Profile by Folate Receptor Status for Vintafolide and Pegylated Liposomal Doxorubicin in Combination, Versus Pegylated Liposomal Doxorubicin Alone, in Platinum-Resistant Ovarian Cancer: Exploratory Analysis of the Phase II PRECEDENT Trial." Int J Gynecol Cancer, 2016;26(9):1580-1585. PMID: 27654255.
- [pubmed] Kraus VB, et al. "Direct in vivo evidence of activated macrophages in human osteoarthritis." Osteoarthritis Cartilage, 2016;24(9):1613-21. PMID: 27084348.
- [review] Maurer AH, et al. "Imaging the folate receptor on cancer cells with 99mTc-etarfolatide: properties, clinical use, and future potential of folate receptor imaging." J Nucl Med, 2014;55(5):701-4. PMID: 24732155.
- [review] Serpe L, et al. "Targeted treatment of folate receptor-positive platinum-resistant ovarian cancer and companion diagnostics, with specific focus on vintafolide and etarfolatide." Pharmgenomics Pers Med, 2014;7:31-42. PMID: 24516337.
- [review] Ledermann JA, et al. "Targeting the folate receptor: diagnostic and therapeutic approaches to personalize cancer treatments." Ann Oncol, 2015;26(10):2034-43. PMID: 26063635.
- [pubmed] Leamon CP, et al. "Synthesis and biological evaluation of EC20: a new folate-derived, (99m)Tc-based radiopharmaceutical." Bioconjug Chem, 2002;13(6):1200-10. PMID: 12440854.
- [pubmed] Turk MJ, et al. "Folate-targeted imaging of activated macrophages in rats with adjuvant-induced arthritis." Arthritis Rheum, 2002;46(7):1947-55. PMID: 12124880.
- [pubmed] Reddy JA, et al. "Preclinical evaluation of (99m)Tc-EC20 for imaging folate receptor-positive tumors." J Nucl Med, 2004;45(5):857-66. PMID: 15136637.
- [pubmed] Müller C, et al. "Effects of the antifolates pemetrexed and CB3717 on the tissue distribution of (99m)Tc-EC20 in xenografted and syngeneic tumor-bearing mice." Mol Pharm, 2010;7(2):597-604. PMID: 20199053.
Sources & Citations
Studies were read from their PubMed abstracts on October 29, 2026; trial registrations from ClinicalTrials.gov and status from Drugs@FDA the same day; the EMA medicines list and PubChem on October 28, 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.