What Is Flotufolastat? Definition and What Research Reports

Definition

Flotufolastat — written in the literature as flotufolastat F 18, (18)F-flotufolastat or [18F]flotufolastat — is a fluorine-18–labelled diagnostic radiopharmaceutical that binds prostate-specific membrane antigen (PSMA) and is imaged using positron emission tomography (PET). It is administered as an intravenous imaging agent so that tissue expressing PSMA, such as many prostate cancer lesions, can be visualised on a PET scan, typically combined with CT or MRI. A post hoc analysis of two phase 3 trials described it explicitly as a PSMA-targeting PET radiopharmaceutical and characterised its distribution in normal organs (PMID 39583908). This page is for educational purposes only and is not medical advice; consult a licensed physician for any question about diagnosis, imaging or treatment.

What Class of Molecule Is It?

Flotufolastat belongs to the family of PSMA-targeting ligands, not to the class of therapeutic or hormone-like peptides that many readers encounter elsewhere in peptide glossaries. Chemically it is a small, synthetic, urea-based PSMA binder attached to a radiohybrid chelator scaffold (the compound is also referred to in older literature under the rhPSMA-7.3 research designation) that allows labelling with fluorine-18. Because it is grouped with other targeted radioligands — molecules that pair a targeting unit with a radionuclide — it often appears in reading lists alongside peptide-receptor radioligands, which is the main reason the term surfaces in peptide-adjacent reference material.

The functional logic is the same as for peptide-receptor imaging agents: a binding unit recognises a cell-surface target, and a radioactive label makes that binding visible. Here the target is PSMA, a transmembrane protein expressed at high levels on many prostate cancer cells, and the label is fluorine-18, a positron emitter with a roughly two-hour physical half-life that suits centralised production and PET acquisition.

Where the Term Comes From

"Flotufolastat" is the international nonproprietary name assigned to the compound; the marketed diagnostic product is known by a separate brand name. A 2023 drug-profile article in Molecular Diagnosis & Therapy documented flotufolastat F 18 as a diagnostic agent receiving its first approval, summarising the development milestones that led to that decision (PMID 37439946). Because the agent is regulated as a diagnostic radiopharmaceutical rather than a research chemical, published work about it comes almost entirely from registrational trials, post hoc analyses of those trials and imaging-technologist literature — for example a 2025 overview of prostate cancer imaging with (18)F-flotufolastat aimed at nuclear medicine technologists (PMID 41188044).

How the Term Is Used in Research

In the published record the word almost always appears as a modifier for a scan: an "(18)F-flotufolastat PET/CT" or "[18F]flotufolastat PET/MRI". Two phase 3 prospective multicenter studies — referred to in the literature as LIGHTHOUSE (newly diagnosed disease) and SPOTLIGHT (biochemical recurrence) — supply the data behind most secondary analyses. Researchers have used the term in at least four recurring contexts:

• Detection of disease sites in men with newly diagnosed or recurrent prostate cancer.
• Reader performance, meaning how consistently different radiologists, or the same radiologist on separate occasions, interpret the same images.
• Biodistribution, meaning where the tracer normally accumulates in non-tumour tissue, including urinary activity that can complicate pelvic reading.
• Prognostic and quantitative imaging metrics derived from the scan, such as tumour volume measurements.

What the Published Literature Reports

The studies below are described at the level of what each one set out to measure. No detection rates, administered activities or performance percentages are reproduced here.

Registrational and post hoc trial work

Reproducibility was assessed directly: the study of interreader and intrareader agreement drew on image interpretations from two phase 3 prospective multicenter studies in patients with newly diagnosed or recurrent prostate cancer (PMID 38871390). Within SPOTLIGHT, researchers reported on true-positive (18)F-flotufolastat lesions specifically in men whose baseline conventional imaging had been negative (PMID 38782456), and a separate exploratory analysis examined how clinical factors related to detection rates in men with recurrent disease (PMID 39104875). A subgroup report described findings in African American patients with suspected recurrence enrolled in the same phase 3 study (PMID 39188996). Bone uptake received its own evaluation, in which researchers assessed the positive predictive value of bone findings using SPOTLIGHT data (PMID 39230406).

Biodistribution and image-quality questions

Two analyses addressed where the tracer goes in non-tumour tissue. A post hoc analysis of LIGHTHOUSE and SPOTLIGHT characterised the normal-organ distribution of the agent (PMID 39583908), while another post hoc analysis of the same two trials quantitatively and qualitatively assessed urinary activity on (18)F-flotufolastat PET/CT in patients with prostate cancer (PMID 37932609). A 2026 report went further, making an intra-patient contemporaneous comparison of (18)F-piflufolastat and (18)F-flotufolastat urinary radioactivity and pelvic region detection rates in men with low-PSA biochemical recurrence after radical prostatectomy (PMID 41729277). Urinary activity matters because bladder and ureteric signal sits anatomically close to the prostate bed, where recurrence is often sought.

Histopathologic and prognostic correlation

More recent work has paired the scan with tissue and with outcomes. A 2026 study correlated [18F]flotufolastat PET/MRI findings in patients with suspected prostate cancer against histopathologic biopsy results (PMID 41290371). In the metastatic castration-resistant setting, researchers examined whether baseline (18)F-flotufolastat PET bone tumour volume prognosticated severe haematologic toxicity in patients receiving (177)Lu-PSMA-targeted radioligand therapy (PMID 40383857).

Adverse Events and Toxicity: What Studies Report

The verified literature summarised here is oriented toward diagnostic performance and biodistribution rather than tolerability, so it does not support statements about the side-effect profile of the imaging agent itself. The one toxicity-related paper concerns a different exposure: it evaluated baseline (18)F-flotufolastat PET bone tumour volume as a prognostic marker for severe haematologic toxicity in men with metastatic castration-resistant prostate cancer who went on to receive (177)Lu-PSMA-targeted radioligand therapy, meaning the toxicity under study followed the therapeutic radioligand, not the diagnostic scan (PMID 40383857). Prescribing information for approved diagnostic radiopharmaceuticals, rather than this page, is the appropriate source for tolerability and radiation-dosimetry detail.

Limits of This Entry

This is a definitional reference, not a clinical summary. Administered activity, uptake time, scan protocol, patient selection and interpretation criteria are all decided by qualified clinicians and are outside the scope of a glossary entry. Flotufolastat is a regulated diagnostic product used in supervised imaging settings; it is not a research chemical, a supplement, or a compound an individual manages independently. Readers comparing it with other PSMA agents should note that head-to-head data are limited — the intra-patient comparison with (18)F-piflufolastat focused narrowly on urinary radioactivity and pelvic region detection in men with low-PSA biochemical recurrence after radical prostatectomy (PMID 41729277).

References

• Prostate Cancer Imaging with (18)F-Flotufolastat (Journal of Nuclear Medicine Technology, 2025)
• Flotufolastat F 18: Diagnostic First Approval (Molecular Diagnosis & Therapy, 2023)
• Interreader and Intrareader Reproducibility of (18)F-Flotufolastat Image Interpretation in Patients with Newly Diagnosed or Recurrent Prostate Cancer: Data from Two Phase 3 Prospective Multicenter Studies (Journal of Nuclear Medicine, 2024)
• Quantitative and Qualitative Assessment of Urinary Activity of (18)F-Flotufolastat-PET/CT in Patients with Prostate Cancer: a Post Hoc Analysis of the LIGHTHOUSE and SPOTLIGHT Studies (Molecular Imaging and Biology, 2024)
• True-Positive (18)F-Flotufolastat Lesions in Patients with Prostate Cancer Recurrence with Baseline-Negative Conventional Imaging: Results from the Prospective, Phase 3, Multicenter SPOTLIGHT Study (Journal of Nuclear Medicine, 2024)
• (18)F-Flotufolastat Positron Emission Tomography in African American Patients With Suspected Prostate Cancer Recurrence: Findings From the Phase 3 SPOTLIGHT Study (Advances in Radiation Oncology, 2024)
• Impact of Clinical Factors on (18)F-Flotufolastat Detection Rates in Men With Recurrent Prostate Cancer: Exploratory Analysis of the Phase 3 SPOTLIGHT Study (Advances in Radiation Oncology, 2024)
• [(18)F]Flotufolastat PET/MRI in Patients with Suspected Prostate Cancer: Correlation with Histopathologic Biopsy Results (Journal of Nuclear Medicine, 2026)
• Impact of baseline (18)F-flotufolastat PET bone tumor volume for prognosticating severe hematologic toxicity in patients with metastatic castration-resistant prostate cancer receiving (177)Lu-PSMA-targeted radioligand therapy (European Journal of Nuclear Medicine and Molecular Imaging, 2025)
• Normal-organ distribution of PSMA-targeting PET radiopharmaceutical (18)F-flotufolastat: a post hoc analysis of the LIGHTHOUSE and SPOTLIGHT studies (American Journal of Nuclear Medicine and Molecular Imaging, 2024)
• PPV of Bone Uptake of (18)F-Flotufolastat: Evaluation Using SPOTLIGHT Study Data (AJR American Journal of Roentgenology, 2024)
• An intra-patient contemporaneous comparison of (18)F-piflufolastat and (18)F-flotufolastat urinary radioactivity and pelvic region detection rates in men with low PSA biochemical recurrence of prostate cancer after radical prostatectomy (European Journal of Nuclear Medicine and Molecular Imaging, 2026)