Piflufolastat F-18

DCFPyL is a low-molecular-weight urea-based PSMA inhibitor rather than a peptide chain, carrying fluorine-18 on a fluoropyridine group. It binds PSMA with nanomolar affinity, internalises with the receptor, and produces high tumour-to-background contrast. Fluorine-18's 109.8-minute half-life and cyclotron production allow centralised manufacture and same-day shipping, which is the reason it displaced gallium tracers in many markets. Its higher positron yield and shorter positron range also give slightly better spatial resolution than gallium-68. Head-to-head studies show broadly comparable detection performance to 68Ga-PSMA-11, with some differences in benign bone uptake that experienced readers learn to discount.

Targets: Prostate-specific membrane antigen (PSMA / FOLH1)

• · 333 MBq (9 mCi) as a bolus followed by saline flush. Patients void immediately before imaging.

Work out your exact syringe units →

• very commonNo clinically meaningful pharmacologic effects— Injected mass is microgram-scale.
• very commonDiagnostic radiation exposure— Comparable to other PET tracers.
• rareHeadache, dysgeusia or fatigue— Reported at around 1 percent or less.

• None absolute. The meaningful risk is a false positive leading to unnecessary treatment, particularly benign bone uptake that can mimic metastasis.

• redundantga-68-psma-11 — Same clinical question, different isotope; choice comes down to supply and reader preference.
• synergylu-177-vipivotide-tetraxetan — Widely used in practice to assess PSMA expression before radioligand therapy, though Locametz holds the formal companion-diagnostic label.

• · No laboratory monitoring required.
• · PSA and PSA doubling time at the time of scan, since these drive pretest probability.
• · Correlate equivocal bone findings with CT or MRI before calling metastatic disease.

FDA approved. Nuclear medicine only; distributed by licensed PET radiopharmacies.

• Morris et al. 2021, CONDOR phase 3 trial of 18F-DCFPyL PET in biochemically recurrent prostate cancer, Clinical Cancer Research (trial)
• Pienta et al. 2021, OSPREY trial of 18F-DCFPyL for staging prostate cancer, Journal of Urology (trial)
• FDA prescribing information for Pylarify (label)

DCFPyL is the smallest molecule in this class and the least peptide-like, which is worth saying plainly because it sits in a peptide catalogue on the strength of its warhead rather than its chemistry. The binding is the same urea transition-state mimicry against PSMA's zinc active site. What differs is the physics and the manufacturing. Fluorine-18 emits a lower-energy positron than gallium-68, so the mean positron range in tissue is shorter — roughly 0.6 mm versus about 3.5 mm at maximum for gallium — and that translates into slightly sharper images, which matters most for small nodes. Fluorine-18 also has a higher positron branching fraction and a 109.8-minute half-life, so a single cyclotron batch produces many patient doses that can be driven to sites hours away. That is the entire commercial logic of the product. Clinically the interpretive burden is the same as for the gallium tracers with one wrinkle: DCFPyL has a reported tendency towards benign, often solitary, PSMA-avid bone findings that are not metastases. Experienced readers discount low-grade solitary rib and pelvic uptake without a CT correlate; inexperienced readers do not, and that is the specific way this tracer generates harm.

Benign bone uptake is the recurring problem with this specific tracer, and it is not a theoretical one — a solitary faint rib or pelvic focus with no CT correlate has been enough to move men from curative-intent local therapy to lifelong systemic therapy. The rule that experienced readers use is that a bone finding without a morphological correlate on the CT, in isolation, and with normal alkaline phosphatase, is more likely benign than not. Beyond that, the same pitfalls as the gallium tracers apply: ganglia, PSMA-expressing non-prostate tumours, and inflammation. On the logistics side, the 110-minute half-life is generous compared with gallium but still unforgiving — a patient who arrives an hour late can cost the dose, and the pharmacy schedules around a fixed calibration time. The broadest failure is the same stage migration problem the whole class creates: PSMA PET reclassifies men as metastatic based on imaging no historical trial used, and the evidence for treating those newly visible deposits is still being built.

• Prostate-specific membrane antigen (PSMA / FOLH1) — Low nanomolar; DCFPyL is generally reported as one of the higher-affinity PSMA ligands, with published inhibition constants in the low single-digit nanomolar range

  Active-site binding followed by internalisation, producing high tumour-to-background contrast at 60 minutes.

• Physiological PSMA in kidney, liver, lacrimal and salivary glands and small bowel — Normal tissue expression

  Expected normal uptake — kidneys take 16.5 percent of administered activity within 60 minutes, liver 9.3 percent, lung 2.9 percent.

• PSMA in benign bone lesions and ganglia — Variable low-level expression

  The specific false-positive signature of this tracer. Solitary low-grade bone uptake without a CT correlate is usually benign.

• CONDOR Phase 3 · n=208 · 2021

  Correct localisation rate — concordance of 18F-DCFPyL PET/CT with a composite standard of truth — in men with biochemical recurrence and uninformative baseline imaging. The lower bound of the confidence interval exceeded the pre-specified threshold for all three blinded readers, and management changed in roughly two-thirds of patients.

• OSPREY Phase 2/3 · n=385 · 2021

  Specificity and sensitivity for pelvic nodal metastasis against histopathology in high-risk patients before prostatectomy (cohort A), and detection of metastatic lesions in cohort B. Specificity was high, sensitivity substantially lower — the honest limitation of any PET against nodal micrometastasis.

Injection with saline flush, 60 minutes of uptake with a permissible window of 60 to 120 minutes, then about 20 to 30 minutes of scanning. Patients void immediately before imaging. Whole visit around 90 minutes to two hours, which is faster than the gallium tracers because the uptake window is tighter.

There is nothing to stack. The injected mass is micrograms and there is no pharmacology to interact with. What does interact is context: androgen deprivation shifts PSMA expression and suppresses PSA at the same time, so hormonal status has to be on the request form. Using this tracer to select for PSMA radioligand therapy is widespread practice, and it is worth being precise about the regulatory position — the formal companion diagnostic label for the lutetium PSMA drug sits with the gallium kits, and eligibility criteria derived from gallium scans are being applied to fluorine-18 scans by analogy. The analogy is reasonable and universal, but it is an analogy. Pairing with multiparametric prostate MRI is genuinely useful for local recurrence in the prostate bed, where PET is weakest because of bladder activity.

Against gallium Ga-68 PSMA-11, the clinical answer is close to identical and the differences are practical. Fluorine-18's 110-minute half-life allows centralised manufacture and shipping, its shorter positron range gives marginally better resolution for small lesions, and its higher positron yield helps count statistics; gallium's advantage is on-site generator production for centres that already have one. Reported differences in benign bone uptake favour gallium slightly on specificity in some series. Against fluciclovine F-18, PSMA imaging is clearly better at low PSA. Against conventional CT and bone scan, there is no contest. Against the therapeutic PSMA radioligand, this shares the warhead but not the chelator or the isotope, and it is used — informally but universally — to decide who gets that therapy.

Not characterised, and not a monthly figure. It is a per-scan charge with separately billed radiopharmaceutical, technical and professional components, and in the US the tracer has been subject to time-limited pass-through payment rules that change what a site actually collects.

• ?Protein binding is not reported in the label's pharmacokinetics section and is left null rather than estimated.
• ?Binding affinity is described qualitatively. Published inhibition constants for DCFPyL vary with assay and I did not resolve a primary source here.
• ?The CONDOR enrolment of 208 and OSPREY enrolment of 385 are as commonly reported for those trials; I resolved both publication records but not participant-level detail from the full texts.
• ?Positron range figures for fluorine-18 versus gallium-68 come from general PET physics rather than a source resolved in this pass.
• ?The claimed higher rate of benign bone uptake with DCFPyL relative to gallium tracers is a consistent clinical impression and appears in comparative series, but I did not resolve a definitive head-to-head quantification.
• ?The tmax of 0.08 hours represents the end of a bolus injection and is not a reported parameter.

• Diagnostic Performance of 18F-DCFPyL-PET/CT in Men with Biochemically Recurrent Prostate Cancer: Results from the CONDOR Phase III, Multicenter Study Morris MJ, Rowe SP, Gorin MA, et al., Clinical Cancer Research, 2021 · PMID 33622706

  CONDOR. The biochemical recurrence trial that supported approval and produced the two-thirds management-change figure.

• 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) Pienta KJ, Gorin MA, Rowe SP, et al., The Journal of Urology, 2021 · PMID 33634707

  OSPREY. The pre-prostatectomy staging study, and the source of the high-specificity, lower-sensitivity picture that should temper enthusiasm about nodal staging.

• PYLARIFY (piflufolastat F 18) injection — US prescribing information Progenics Pharmaceuticals / Lantheus, FDA prescribing information

  Source of the biphasic decline, the 0.17-hour distribution and 3.47-hour elimination half-lives, the organ distribution percentages and the 50 percent urinary excretion at 8 hours.