Pylclari (Piflufolastat F 18)
Fluorine-18 PSMA-targeted radiopharmaceutical for PET imaging in prostate cancer
Pylclari (piflufolastat F 18), also known as [18F]DCFPyL, is a fluorine-18 labelled radiopharmaceutical used with positron emission tomography (PET) imaging to detect prostate-specific membrane antigen (PSMA)-positive lesions in adult men with prostate cancer. Authorised by the European Medicines Agency in July 2023 and marketed by Curium Pharma, Pylclari supports clinicians in two pivotal scenarios: primary staging of high-risk, hormone-sensitive prostate cancer prior to curative-intent therapy, and localisation of disease in patients with biochemical recurrence evidenced by rising serum prostate-specific antigen (PSA). Its longer physical half-life compared with gallium-68 tracers (approximately 110 versus 68 minutes) enables centralised cyclotron production and regional distribution, broadening patient access to high-resolution PSMA PET imaging.
Quick Facts
Key Takeaways
- Pylclari contains piflufolastat (18F), a fluorine-18 labelled small-molecule ligand that binds with high affinity to prostate-specific membrane antigen (PSMA) on prostate cancer cells.
- It is authorised in the European Union for PET detection of PSMA-positive lesions in adult men with prostate cancer in two settings: primary staging before curative-intent therapy and localisation of suspected recurrence based on rising PSA.
- Administration involves a single intravenous injection of approximately 333 MBq (9 mCi) performed in a licensed nuclear medicine facility, with PET imaging started 60 to 120 minutes after injection.
- Pivotal trials (OSPREY for primary staging, CONDOR for biochemical recurrence) demonstrated high positive predictive value and strong clinical utility, with PSMA PET frequently changing intended management.
- Pylclari is generally very well tolerated; the most common side effects in clinical studies were headache, altered taste (dysgeusia), and fatigue, all typically mild and self-limiting.
What Is Pylclari and What Is It Used For?
Pylclari is a radiopharmaceutical diagnostic agent – a medicine that contains a radioactive isotope and is used exclusively to generate medical images, not to treat disease. The product is a clear, colourless to slightly yellow sterile solution for intravenous injection supplied at a radioactive concentration of 1,000 megabecquerels per millilitre (MBq/mL) at reference time. The active substance is piflufolastat (18F), a synthetic small molecule labelled with the positron-emitting radionuclide fluorine-18.
The molecule binds selectively to the extracellular domain of prostate-specific membrane antigen, a transmembrane glycoprotein (also known as glutamate carboxypeptidase II) that is expressed at low levels in normal prostate tissue but dramatically overexpressed on the surface of most prostate cancer cells. PSMA expression is typically 100 to 1,000 times higher on malignant prostate tissue compared with benign prostate tissue, and expression increases further with more aggressive disease, in metastatic lesions, and in castration-resistant prostate cancer. This biology makes PSMA an ideal target for molecular imaging.
After intravenous administration, piflufolastat (18F) circulates through the bloodstream and accumulates at sites with high PSMA expression. The fluorine-18 atom undergoes radioactive decay, primarily by positron emission. When each emitted positron encounters an electron, the two particles annihilate and produce a pair of 511 keV gamma photons travelling in opposite directions. PET scanners detect these coincident photons to reconstruct a three-dimensional map of tracer uptake, revealing the location and extent of PSMA-positive disease throughout the body.
Pylclari received marketing authorisation from the European Commission in July 2023 following a positive opinion from the European Medicines Agency (EMA). The active substance is chemically identical to piflufolastat (18F) approved in the United States as Pylarify in May 2021. Curium Pharma, which holds the European marketing authorisation, distributes Pylclari through its network of PET manufacturing facilities across Europe, enabling same-day delivery of individual patient doses.
Approved Indications
Pylclari is indicated in adult men with prostate cancer for the detection of PSMA-positive lesions with PET in two clinically distinct scenarios:
- Primary staging of high-risk prostate cancer: In men newly diagnosed with prostate cancer who are candidates for initial definitive therapy (radical prostatectomy or radiotherapy), Pylclari PET imaging helps determine whether disease has spread beyond the prostate, particularly to pelvic lymph nodes or distant sites. Accurate staging informs the selection and extent of local treatment and may identify patients in whom curative-intent therapy should be reconsidered.
- Suspected recurrence based on rising PSA: In men who have been previously treated for prostate cancer and show biochemical evidence of recurrence (rising serum PSA), Pylclari PET imaging is used to localise the site of recurrent disease. Early and precise localisation enables targeted salvage therapies such as focal radiotherapy or metastasis-directed treatment, potentially improving outcomes and delaying systemic therapy.
How PSMA PET Imaging Works
Prostate-specific membrane antigen was originally identified on the surface of prostate epithelial cells but is now recognised as a cell-surface enzyme expressed on many solid tumours, with the highest and most consistent overexpression in prostate adenocarcinoma. PSMA expression rises along a continuum from normal prostate tissue to high-grade intraepithelial neoplasia, localised adenocarcinoma, regional lymph node metastases, and distant metastatic disease. Importantly, PSMA expression remains high or increases further in castration-resistant disease, where conventional imaging is often limited.
When piflufolastat (18F) is administered intravenously, the molecule rapidly distributes throughout the body. Its PSMA-binding portion, derived from glutamate-urea-lysine chemistry, docks into the active site of the PSMA enzyme with nanomolar affinity. The radiotracer is internalised by PSMA-expressing cells, increasing intracellular retention and improving lesion contrast on PET images acquired 60 to 120 minutes after injection.
Physiological uptake of piflufolastat (18F) occurs in organs and tissues that naturally express PSMA, including the salivary and lacrimal glands, kidneys, proximal small intestine, liver, and spleen. The tracer is predominantly cleared by the kidneys into the urinary bladder, which is why adequate hydration and voiding protocols are essential to minimise radiation dose to the bladder wall and reduce interference with interpretation of pelvic structures. PET/CT or PET/MRI hybrid imaging combines the functional information from PSMA uptake with detailed anatomical reference, providing a comprehensive assessment of disease distribution.
PSMA PET imaging has reshaped prostate cancer management worldwide. The proPSMA randomised trial demonstrated that PSMA PET/CT has significantly higher accuracy than combined CT plus bone scan for primary staging of high-risk disease (92% versus 65%). Observational data from the CONDOR and OSPREY trials, which formed the basis of Pylclari’s regulatory approval, showed that PSMA PET changes intended management in 54–76% of patients, often by redirecting therapy from local to systemic approaches or from palliative to targeted salvage.
What Should You Know Before Receiving Pylclari?
Although Pylclari is a single-dose diagnostic agent rather than a chronic therapy, safe and accurate imaging depends on appropriate patient preparation, a thorough clinical history, and careful communication with the nuclear medicine team. Several considerations influence both patient safety and the diagnostic value of the scan. These should be addressed during scheduling and during the pre-injection interview on the day of the examination.
Contraindications
The European summary of product characteristics for Pylclari identifies the following contraindication:
- Hypersensitivity to the active substance or to any of the excipients: Patients with known hypersensitivity to piflufolastat (18F) or to any component of the formulation (including the ethanol solvent and ascorbic acid stabiliser in the finished product) must not receive Pylclari.
In addition to this labelled contraindication, the benefit–risk balance of the procedure should be carefully evaluated in any individual patient. As with all radiopharmaceuticals, the diagnostic benefit must justify the radiation exposure.
Warnings and Precautions
Several important warnings and precautions apply to PSMA PET imaging with Pylclari:
Risk of image misinterpretation: PSMA expression is not exclusive to prostate cancer. Physiological uptake is observed in the salivary glands, kidneys, liver, spleen, and bowel, and pathological uptake can occur in benign conditions (such as Paget’s disease, granulomatous inflammation, and some fractures) and in non-prostatic malignancies (including renal cell, thyroid, and breast cancers, and PSMA-positive neovasculature of various solid tumours). Conversely, some prostate cancer lesions, particularly those that are neuroendocrine-differentiated, poorly differentiated, or heavily pre-treated, may exhibit low or absent PSMA expression, leading to false-negative scans. Image interpretation should be performed by appropriately trained nuclear medicine physicians with experience in PSMA PET and should always be integrated with the patient’s clinical history, histopathology, serum PSA trajectory, and other imaging findings.
Radiation exposure: Pylclari contributes to the patient’s cumulative lifetime radiation exposure. The effective radiation dose from a typical Pylclari administration (approximately 333 MBq) is estimated at about 5 to 6 millisieverts (mSv). When combined with a low-dose CT component of a PET/CT examination, the total effective dose is generally in the range of 8 to 12 mSv, which is comparable to other clinical nuclear medicine procedures and well within accepted limits for diagnostic imaging. The justification and optimisation principles of radiation protection (as codified in European Council Directive 2013/59/Euratom) must always be applied. The lowest activity compatible with obtaining diagnostic-quality images should be used.
Renal impairment: Because piflufolastat (18F) is primarily eliminated through the kidneys, patients with severely impaired renal function may experience delayed tracer clearance, increased background activity, and potentially altered image quality. Adequate hydration is especially important in this group. Imaging protocols may need to be adapted to accommodate renal impairment, and the nuclear medicine team should be informed of any significant kidney disease or dialysis schedule prior to the appointment.
Impact of prostate cancer therapies: Hormonal therapies and other systemic treatments for prostate cancer can modulate PSMA expression and thereby alter tracer uptake. Androgen receptor pathway inhibitors (such as enzalutamide, apalutamide, and darolutamide) and androgen deprivation therapy (ADT) with GnRH agonists or antagonists have complex, time-dependent effects on PSMA expression. Short-term ADT initiation has been associated with a transient increase (“flare”) in PSMA expression, while prolonged therapy can reduce expression in some lesions. Newer androgen receptor inhibitors may also have variable effects. The timing of the PET scan relative to therapy changes should be discussed with the treating oncologist, and all current and recent systemic therapies should be documented on the imaging request.
Pregnancy and Breastfeeding
Pylclari is indicated for use in adult men with prostate cancer. Accordingly, considerations for pregnancy and breastfeeding are primarily operational rather than clinical for the treated patient, but they remain important for staff and close contacts:
- Female healthcare workers who are pregnant, think they may be pregnant, or are breastfeeding should follow local radiation protection protocols when handling Pylclari or caring for patients who have recently received the injection.
- Male patients scheduled for Pylclari PET imaging should inform the nuclear medicine team if they have a pregnant partner at home, so appropriate post-procedure contact advice can be provided.
- Patients should be advised to avoid close, prolonged contact with young children and pregnant women for a short period after the scan, following the specific guidance given by the imaging facility.
After receiving Pylclari you will emit low levels of radiation for several hours. Follow all post-procedure instructions from the nuclear medicine staff, including advice on contact with others, particularly pregnant women and small children. Drink plenty of fluids and void frequently in the first few hours after the injection to accelerate urinary elimination of the tracer and to reduce radiation dose to your bladder. Most tracer activity will have decayed to negligible levels within 10 to 12 hours.
How Does Pylclari Interact with Other Drugs?
Unlike conventional medicines that are metabolised by hepatic enzymes or excreted through the kidneys over days to weeks, Pylclari is administered as a single, sub-pharmacological mass dose of active substance and decays rapidly via radioactive half-life. There is no meaningful hepatic metabolism to interact with cytochrome P450 enzymes, no transporter interactions of clinical significance, and no accumulation in the body. As a result, traditional drug–drug interaction concerns do not apply.
The clinically important interactions relate instead to how other prostate cancer therapies can modulate the biological target of the tracer. Changes in PSMA expression on prostate cancer cells can increase or decrease tracer uptake on PET imaging, with implications for lesion detectability and interpretation. Awareness of these effects enables the nuclear medicine team to time the scan appropriately and to integrate treatment history into the image report.
Major Interactions
Androgen receptor pathway modulation represents the most clinically relevant category of interactions with PSMA PET imaging. Several agents in this class may influence tracer distribution and lesion conspicuity:
| Drug or Class | Effect on PSMA Imaging | Clinical Recommendation |
|---|---|---|
| GnRH agonists and antagonists (leuprolide, goserelin, degarelix, relugolix) | Transient “flare” increase in PSMA expression shortly after initiation; may reduce uptake over prolonged therapy | Document therapy start date; consider scan timing relative to initiation |
| Androgen receptor inhibitors (enzalutamide, apalutamide, darolutamide) | Variable, time-dependent changes in PSMA expression on cancer cells | Report current treatment and duration on the imaging request |
| Abiraterone acetate | May modulate PSMA expression through androgen biosynthesis inhibition | Inform nuclear medicine physician of ongoing therapy |
| Chemotherapy (docetaxel, cabazitaxel) | Response to treatment may reduce PSMA-avid tumour burden; dedifferentiation may lower expression | Consider post-treatment scan timing and integrate with biochemical response |
Minor Interactions
Several other medicines and substances can have minor, mostly theoretical effects on PSMA PET imaging quality or interpretation. These rarely require dose modification or scan rescheduling but should be known to the imaging team:
| Drug or Class | Potential Effect | Clinical Recommendation |
|---|---|---|
| Diuretics (furosemide, thiazides) | May accelerate urinary excretion; useful to reduce bladder activity but must be balanced against dehydration risk | Continue or adjust per imaging protocol; ensure adequate hydration |
| 5-Alpha reductase inhibitors (finasteride, dutasteride) | Minimal documented effect on PSMA expression or tracer kinetics | Document use; no specific scan preparation needed |
| Corticosteroids | High-dose systemic steroids may theoretically influence PSMA expression; clinical impact uncertain | Record dose and duration on the request form |
| Immunotherapy (immune checkpoint inhibitors) | Immune-related inflammatory changes can mimic PSMA-positive disease on imaging | Discuss recent treatment cycles with reporting physician |
No formal pharmacokinetic drug–drug interaction studies have been conducted with Pylclari. The interactions summarised above are based on the known biology of PSMA expression and the mechanisms of action of prostate cancer therapies. Provide your full medication history, including over-the-counter medicines, herbal products, and recent dose changes, to the nuclear medicine team before your scan to support accurate image interpretation.
What Is the Correct Dosage of Pylclari?
Pylclari is not a medicine that patients self-administer, and the concept of a prescription that the patient fills at a pharmacy does not apply. Each dose is dispensed by a specialised radiopharmacy or PET manufacturing centre, delivered to the imaging facility under controlled conditions, and injected by trained staff immediately prior to imaging. The dose is measured in units of radioactivity (megabecquerels, MBq, or millicuries, mCi) rather than in milligrams, because the pharmacological effect of the active substance is negligible and it is the radioactivity that enables imaging.
Adults
Recommended Adult Activity
Activity: Approximately 333 MBq (9 mCi) as a single intravenous bolus injection, with an acceptable range of 296 to 370 MBq (8 to 10 mCi).
Volume: Typically delivered in a small volume (up to approximately 10 mL) followed by a saline flush.
Imaging timing: PET image acquisition should commence 60 to 120 minutes after injection; a 90- to 120-minute uptake period is commonly used for optimal lesion contrast.
Image acquisition: Whole-body PET/CT from the vertex of the skull to the mid-thigh, extended to the feet when clinically indicated (for example, suspected bone metastases in the lower limbs).
The precise activity within the recommended range is determined by the nuclear medicine physician, taking into account patient body habitus, the performance characteristics of the PET scanner (including sensitivity, time-of-flight capability, and reconstruction algorithm), clinical question, and institutional protocols. The guiding principle is ALARA (as low as reasonably achievable): the smallest activity that yields diagnostic-quality images should be used to minimise radiation exposure.
Children
Paediatric Dosage
Pylclari is not indicated for use in children or adolescents. Prostate cancer is exceedingly rare in this age group, and the safety and efficacy of piflufolastat (18F) have not been established in paediatric populations. Pylclari should not be administered to patients under 18 years of age outside of appropriately approved research protocols.
Elderly
Geriatric Dosage
No specific dose adjustment is required in elderly patients. Pivotal clinical trials of piflufolastat (18F) included men with a broad age distribution, with substantial representation of patients in their seventies and eighties. Tolerability and image quality in these patients are similar to younger adults. However, attention should be paid to hydration status, renal function, and post-procedure voiding, as elderly men are more likely to have reduced glomerular filtration and urinary symptoms that may slow tracer clearance.
Special Populations
Renal Impairment
Dose adjustments are not formally defined for patients with renal impairment, but image quality may be affected by delayed clearance and increased background activity. Adequate peri-procedural hydration is essential. Dialysis patients and those with stage 4 or 5 chronic kidney disease should be identified in advance so that imaging protocols (timing, acquisition duration, reconstruction) can be optimised.
Hepatic Impairment
No dose adjustment is recommended based on hepatic function. Hepatic clearance does not play a significant role in tracer elimination.
Preparation Before the Scan
Patients undergoing Pylclari PET imaging should follow the preparation instructions provided by the imaging facility. Standard guidance typically includes:
- Hydration: Drink approximately 500 mL of water in the hour before the appointment and continue to hydrate adequately afterwards to promote urinary tracer excretion and reduce bladder dose.
- Voiding: Empty the bladder immediately before image acquisition and frequently during the hours following injection.
- Fasting: No specific fasting is required for PSMA PET (unlike FDG PET, which requires a pre-scan fast). Patients may eat and drink normally.
- Medications: Continue all regular medicines unless specifically advised otherwise by the ordering clinician. Bring a current medication list to the appointment.
- Clothing and metal objects: Wear comfortable clothing; metal items (belts, jewellery, watches) may need to be removed for the CT component of the examination.
Missed Appointment
The notion of a missed dose does not apply to Pylclari in the usual sense, because it is a single diagnostic administration rather than a course of therapy. If a patient is unable to attend their scheduled PSMA PET appointment, the imaging facility must be notified as early as possible. Each patient dose is produced to a specific calibration time and cannot simply be re-used; late cancellation may result in wasted radiopharmaceutical and costs. Rescheduling is usually straightforward once a new production slot is available.
Overdose
Inadvertent administration of more than the intended activity of Pylclari is uncommon and would present primarily as increased radiation exposure rather than a classical pharmacological overdose. There is no specific antidote. Management is guided by radiation protection principles:
- Encourage aggressive oral or intravenous hydration and frequent voiding to accelerate urinary elimination of the tracer.
- Monitor the patient for any clinical symptoms (which are unlikely given the small mass dose of active substance).
- Calculate the estimated effective dose received and consult the local medical physics and radiation protection service for further guidance and documentation.
- Record the event in accordance with institutional and national radiation safety regulations.
What Are the Side Effects of Pylclari?
The safety profile of piflufolastat (18F) has been characterised primarily through two multicentre clinical trials: OSPREY, which evaluated the tracer in men with high-risk prostate cancer prior to radical prostatectomy and in men with metastatic disease, and CONDOR, which focused on patients with biochemical recurrence after prior definitive therapy. Together, these studies enrolled more than 600 patients and supported both the European and United States regulatory submissions. Additional real-world safety data from post-marketing experience with Pylclari and with the chemically identical US product Pylarify further confirm the favourable tolerability of the agent.
Across the combined clinical trial population, the rate of treatment-related adverse events was low. The majority of events were grade 1 (mild) and resolved spontaneously without treatment. No clinically relevant changes in vital signs, electrocardiographic parameters, or routine laboratory values were associated with tracer administration. Severe hypersensitivity reactions to piflufolastat (18F) have been reported only very rarely in post-marketing surveillance.
Common Side Effects
May affect 1 to 10 in 100 patients (1–10%)
- Headache
- Dysgeusia (altered or metallic taste)
- Fatigue
Uncommon Side Effects
May affect 1 to 10 in 1,000 patients (0.1–1%)
- Nausea
- Dizziness
- Injection-site reactions (pain, redness, warmth)
- Flushing
- Pruritus (itching)
- Transient increases in blood pressure
Rare Side Effects
May affect fewer than 1 in 1,000 patients (<0.1%)
- Hypersensitivity reactions (including urticaria and angioedema)
- Chills
- Abdominal discomfort
- Vomiting
- Chest discomfort
Radiation-Related Considerations
Because Pylclari is a radiopharmaceutical, all administrations carry an associated radiation dose. The effective dose from a typical 333 MBq administration is approximately 5 to 6 mSv. For context, the average annual effective dose from natural background radiation in Europe is approximately 2–3 mSv, and a conventional abdominopelvic CT scan delivers approximately 8–10 mSv. The combined PSMA PET/CT examination (tracer plus CT) typically results in a total effective dose in the range of 8 to 12 mSv.
Organs receiving the highest absorbed doses from piflufolastat (18F) include the kidneys, urinary bladder wall, salivary glands, and lacrimal glands, reflecting the physiological expression of PSMA and the predominant renal route of excretion. Adequate peri-procedural hydration and frequent voiding substantially reduce the dose to the bladder wall. The long-term stochastic risk of radiation-induced cancer from a single diagnostic dose is very small and, for appropriately selected patients, is far outweighed by the clinical benefit of accurate disease localisation and treatment planning.
Pregnant women and young children should avoid close, prolonged contact with patients in the first few hours after injection, in line with local radiation protection advice. By approximately 10 to 12 hours after the scan, the tracer activity has decayed to levels indistinguishable from natural background.
When to Seek Medical Attention
Serious adverse reactions to Pylclari are rare, but patients should contact their healthcare provider or seek urgent medical attention if they experience any of the following in the hours or days following the scan:
- Signs of an allergic reaction such as widespread rash, hives, swelling of the face, lips, tongue, or throat, or difficulty breathing (seek emergency care).
- Persistent or severe headache that does not improve with simple analgesia.
- Severe or recurrent nausea or vomiting.
- Marked dizziness, fainting, or palpitations.
- Persistent pain, swelling, or redness at the injection site.
- Any unexpected symptom that causes concern.
Suspected adverse drug reactions should also be reported to the national regulatory authority (for example, the national pharmacovigilance system in your country) and to the marketing authorisation holder, in line with the European Union’s yellow-card style adverse reaction reporting systems.
How Should Pylclari Be Stored?
Pylclari is a radioactive medicinal product that requires specialised handling, storage, and disposal procedures. Patients do not receive take-home supplies of the medicine and are not involved in any aspect of its preparation or storage. All logistics are managed within the radiopharmacy and nuclear medicine department under strict national and European regulations covering radioactive materials and medicinal products.
Key storage and handling conditions for Pylclari include the following:
- Temperature: Store below 25°C in the original shielded container. Do not freeze. Detailed temperature specifications are provided in the Summary of Product Characteristics.
- Radiation shielding: Vials and patient syringes must be kept inside lead shielded containers in designated radioactive material storage areas. Access is restricted to authorised, radiation-trained personnel.
- Expiry and shelf-life: Due to the 109.7-minute physical half-life of fluorine-18, the radioactive concentration decreases rapidly with time. The product is labelled with a reference time of calibration and a strict expiry time beyond which it should not be used. Typical shelf-life from end of synthesis is up to 10–12 hours depending on the formulation; patient doses are used well within this window.
- Quality control: Each batch is subject to radiopharmaceutical quality control, including radiochemical purity (typically ≥95% of activity as the intended compound), pH, sterility, and endotoxin testing, before release for clinical use.
- Disposal: Any unused solution or contaminated materials must be disposed of as radioactive waste in accordance with national regulations. Short half-life products are usually stored in decay-in-storage areas until residual activity is below regulatory thresholds.
For patients, the practical implication is straightforward: because of the short half-life, the timing of your appointment is critical. Delays of more than a few tens of minutes can significantly reduce the available activity and may require rescheduling. Arrive at the agreed check-in time and follow the nuclear medicine team’s guidance regarding preparation and identification procedures.
What Does Pylclari Contain?
Pylclari is supplied as a ready-to-use sterile, pyrogen-free solution for intravenous injection. The product is provided in multi-dose glass vials within lead shielded containers, sized to allow dispensing of one or more patient doses. Individual patient syringes are typically prepared by the radiopharmacy based on the scheduled appointment time and the requested activity.
Active Substance
The active substance is piflufolastat (18F), also known as [18F]DCFPyL (2-(3-(1-carboxy-5-[(6-[18F]fluoropyridine-3-carbonyl)amino]pentyl)ureido)pentanedioic acid). Each millilitre of the finished solution contains 1,000 MBq of radioactivity at reference time, corresponding to sub-microgram amounts of the chemical compound – far below any pharmacologically active concentration.
Fluorine-18 is a positron-emitting radioisotope with a physical half-life of approximately 109.7 minutes. It decays predominantly by positron emission (branching ratio approximately 97%) to stable oxygen-18. The emitted positrons undergo annihilation with electrons to produce pairs of 511 keV gamma photons that are detected in coincidence by PET scanners. Compared with gallium-68 (half-life ~68 minutes), fluorine-18 has a lower mean positron range in tissue, which can translate into slightly better intrinsic spatial resolution on PET images, and its longer half-life permits centralised cyclotron production and regional distribution.
Excipients
The finished product formulation includes excipients that stabilise the radiolabelled compound and maintain an appropriate pH and isotonicity for intravenous administration:
- Ascorbic acid and sodium ascorbate – antioxidants that reduce radiolysis and preserve radiochemical purity during the product’s shelf-life.
- Ethanol – present in small quantities as a residual solvent from the manufacturing and stabilisation process.
- Water for injections – the vehicle for the solution.
Patients should inform the nuclear medicine team if they are aware of any specific allergies to these excipients, although clinically significant hypersensitivity is uncommon.
Appearance
Pylclari is a clear, colourless to slightly yellow solution. Any vial whose contents appear turbid or contain visible particulates should not be used and should be returned to the radiopharmacy for investigation.
Unlike gallium-68, which is produced from a bench-top germanium-68 generator, fluorine-18 is produced in a medical cyclotron by proton bombardment of oxygen-18 enriched water. The radioactive 18F-fluoride is then used to label the PSMA-targeting precursor through a one-step nucleophilic substitution reaction, followed by purification and formulation. This centralised production model enables a single manufacturing site to serve many imaging facilities within a regional transport radius of several hundred kilometres, which has greatly expanded access to PSMA PET imaging across Europe.
Frequently Asked Questions About Pylclari
Pylclari (piflufolastat F 18) is a radioactive diagnostic medicine used with positron emission tomography (PET) scanners to image prostate cancer. It targets prostate-specific membrane antigen (PSMA), a protein that is highly expressed on most prostate cancer cells. Pylclari is authorised in adult men for two indications: primary staging of high-risk prostate cancer before curative-intent therapy (surgery or radiotherapy) and localisation of disease in patients with biochemical recurrence, that is, rising serum PSA after previous treatment. It is not a treatment – it only helps doctors see where prostate cancer cells are located.
On the day of the appointment you will check in at the nuclear medicine department and be asked a short medical and medication history. A nurse or technician will place a small cannula in a vein in your arm and inject approximately 333 MBq of Pylclari as a single bolus followed by a saline flush. You will then rest quietly for 60 to 120 minutes while the tracer circulates and binds to PSMA-positive tissues. Just before imaging you will be asked to empty your bladder. The PET/CT scan itself typically takes 20 to 30 minutes while you lie still on the scanner table. After the scan you can usually go home and resume normal activities, drinking plenty of fluids for the rest of the day.
Pylclari is generally very well tolerated. In clinical trials the most commonly reported side effects were headache, altered or metallic taste (dysgeusia), and fatigue, each occurring in a small proportion of patients and usually mild and short-lived. Less common effects include nausea, dizziness, injection-site reactions, and flushing. Allergic reactions are rare. The main safety issue with any PET tracer is the small radiation dose, which for Pylclari is in the range of 5 to 6 mSv per administration – similar to other nuclear medicine procedures and considered safe in the diagnostic setting.
Pylclari uses fluorine-18 as its radiolabel, while tracers such as gallium-68 PSMA-11 (for example Illuccix and Locametz) use gallium-68. The main practical difference is the half-life: fluorine-18 lasts about 110 minutes, versus 68 minutes for gallium-68. This allows Pylclari to be produced at a central cyclotron and transported to imaging sites hundreds of kilometres away, improving access and scheduling flexibility. Fluorine-18 also produces lower-energy positrons, which can slightly improve image sharpness. For detecting prostate cancer, modern F-18 and Ga-68 PSMA tracers perform very similarly in head-to-head studies; choice often comes down to local availability and radiopharmacy logistics.
No. Pylclari is a diagnostic agent only. It is used to show where PSMA-positive disease is present but does not kill cancer cells or reduce tumour size. The mass of chemical compound injected is so small that it has no pharmacological effect. However, the PSMA target that Pylclari binds is also the basis for therapeutic PSMA radioligand therapies such as lutetium-177 vipivotide tetraxetan (Pluvicto), which deliver cytotoxic beta radiation to cancer cells. A Pylclari PET scan can help identify patients who are likely to benefit from PSMA-targeted therapy by confirming that their cancer expresses PSMA.
Fluorine-18 has a physical half-life of approximately 110 minutes, meaning that every 110 minutes the amount of radioactivity in your body roughly halves. In addition, much of the tracer is excreted in urine within the first few hours. By about 10 to 12 hours after the injection, the activity has decayed and been eliminated to levels that are essentially the same as natural background radiation. To accelerate elimination and reduce bladder dose, drink plenty of water on the day of the scan and void often. Most facilities recommend avoiding prolonged close contact with pregnant women and young children for a few hours after the examination.
PSMA PET with Pylclari is significantly more sensitive and specific than conventional imaging (CT, bone scan) for detecting prostate cancer spread. In many clinical scenarios it has become the preferred imaging modality, and international guidelines including the EAU and NCCN prostate cancer guidelines now endorse PSMA PET for high-risk primary staging and biochemical recurrence. However, it is not always a complete replacement: multi-parametric prostate MRI remains the key tool for local tumour assessment and biopsy planning within the prostate itself, and contrast-enhanced CT or MRI may still be required for specific clinical questions. The optimal imaging strategy is individualised and usually decided in a multidisciplinary setting.
Usually not, but the decision should be made jointly by your urologist or oncologist and the nuclear medicine team. Hormonal therapies and androgen receptor inhibitors can change PSMA expression on cancer cells, which may influence the appearance of the scan. In many cases the scan is intentionally performed either before starting these therapies or after a well-defined interval, so that the images best answer the clinical question. Do not stop any prescribed medicine without first discussing it with the doctor who prescribed it.
References
This article is based on the following peer-reviewed sources and official medical guidelines:
- European Medicines Agency. Pylclari (piflufolastat [18F]): EPAR – Product Information. European Commission marketing authorisation granted 21 July 2023. EMA/CHMP/193019/2023.
- U.S. Food and Drug Administration. Pylarify (piflufolastat F 18) Injection Prescribing Information. Approved May 2021; updated label.
- Pienta KJ, Gorin MA, Rowe SP, et al. A Phase 2/3 Prospective Multicenter Study of the Diagnostic Accuracy of Prostate Specific Membrane Antigen PET/CT with 18F-DCFPyL in Prostate Cancer Patients (OSPREY). Journal of Urology. 2021;206(1):52–61. doi:10.1097/JU.0000000000001698
- Morris MJ, Rowe SP, Gorin MA, et al. Diagnostic Performance of 18F-DCFPyL-PET/CT in Men with Biochemically Recurrent Prostate Cancer: Results from the CONDOR Phase III, Multicenter Study. Clinical Cancer Research. 2021;27(13):3674–3682. doi:10.1158/1078-0432.CCR-20-4573
- Hofman MS, Lawrentschuk N, Francis RJ, et al. Prostate-specific membrane antigen PET-CT in patients with high-risk prostate cancer before curative-intent surgery or radiotherapy (proPSMA): a prospective, randomised, multicentre study. The Lancet. 2020;395(10231):1208–1216. doi:10.1016/S0140-6736(20)30314-7
- Fendler WP, Eiber M, Beheshti M, et al. PSMA PET/CT: Joint EANM Procedure Guideline/SNMMI Procedure Standard for Prostate Cancer Imaging 2.0. European Journal of Nuclear Medicine and Molecular Imaging. 2023;50(5):1466–1486. doi:10.1007/s00259-022-06089-w
- Mottet N, van den Bergh RCN, Briers E, et al. EAU-EANM-ESTRO-ESUR-SIOG Guidelines on Prostate Cancer. European Association of Urology. 2024 Edition.
- National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Prostate Cancer. Version 4.2025.
- Sartor O, de Bono J, Chi KN, et al. Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer. New England Journal of Medicine. 2021;385(12):1091–1103. doi:10.1056/NEJMoa2107322
- Jadvar H, Calais J, Fanti S, et al. Appropriate Use Criteria for Prostate-Specific Membrane Antigen PET Imaging. Journal of Nuclear Medicine. 2022;63(1):59–68. doi:10.2967/jnumed.121.263262
- Perera M, Papa N, Roberts M, et al. Gallium-68 Prostate-specific Membrane Antigen Positron Emission Tomography in Advanced Prostate Cancer – Updated Diagnostic Utility, Sensitivity, Specificity, and Distribution of Prostate-specific Membrane Antigen-avid Lesions: A Systematic Review and Meta-analysis. European Urology. 2020;77(4):403–417. doi:10.1016/j.eururo.2019.01.049
- World Health Organization (WHO). WHO Model List of Essential Medicines. 23rd List, 2023.
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