PET-CT · Prostate cancer · Journal update
F-18 Fluciclovine PET/CT for PSMA-Negative Biochemical Recurrence
A different biological signal can reveal recurrence that PSMA imaging does not show.
01 · The basic science
What is F-18 fluciclovine?
Fluciclovine, also called 18F-FACBC and marketed as Axumin, is a fluorine-18-labelled synthetic amino acid analogue. Cells take it up through amino acid transporters, including ASCT2 and LAT1. Its uptake does not depend on PSMA expression.[3]
Think of three different questions: PSMA imaging asks about a cell-surface target; FDG asks about glucose use; fluciclovine asks about amino acid transport. Fluciclovine is not incorporated into proteins, so the scan should not be described as a direct measurement of protein synthesis.[4]
A negative PSMA scan alone does not prove that a tumour lacks PSMA. Disease may be microscopic, have low target expression or be obscured by background activity.[5]
02 · Three tracers, three signals
PSMA, FDG and fluciclovine
| Feature | PSMA PET/CT | F-18 FDG PET/CT | F-18 fluciclovine PET/CT |
|---|---|---|---|
| Signal | Binding to PSMA, a cell-surface protein. | Glucose transport via GLUT and intracellular phosphorylation. | Amino acid transport via ASCT2 / LAT1. |
| Main role here | Preferred test for most BCR, especially nodal and distant disease. | Selected aggressive, poorly differentiated or suspected neuroendocrine disease. | Alternative when PSMA imaging is unavailable; complementary in selected PSMA-negative BCR. |
| Practical strength | Generally higher detection at low PSA than fluciclovine. | May reveal metabolically active disease with low PSMA uptake. | Low early bladder activity can help assess the prostate bed. |
| Key limit | Small or low-PSMA lesions may be missed; benign uptake also occurs. | Often low yield in typical low-PSA BCR; inflammation can be avid. | Lower overall detection than PSMA in early BCR; benign and other malignant uptake occurs. |
| Background | Salivary glands, kidneys and bowel; urinary activity varies by agent. | Brain, variable myocardium and muscle, and urinary tract. | Pancreas, liver, marrow and muscle; urinary uptake can still occur. |
“PSMA PET” includes several tracers. Renally excreted agents may obscure pelvic findings; the same urinary pattern does not apply to every PSMA tracer.[5]
In a separate 2019 prospective paired study of 50 men with early BCR after prostatectomy (PSA 0.2–2.0 ng/mL), detection was 56% with Ga-68 PSMA-11 and 26% with fluciclovine. That population differs from the selected PSMA-negative cohort below.[6]
03 · Original research · Published online 29 October 2026
What did the new JNM study find?
Szidonya and colleagues prospectively studied 50 patients with BCR, PSA ≥0.2 ng/mL and negative PSMA PET. Fluciclovine PET/CT followed within 30 days.[1]
The abstract reports detection rising from 44% at PSA 0.2–0.5 ng/mL to 100% at ≥5 ng/mL. Subgroup denominators are not given there; 100% is not a guarantee for an individual patient. Only 14 patients had an available reference standard; positive findings in that subset were confirmed.[1]
What these results do—and do not—establish
This is a small, single-centre, single-arm study. A 56% positivity rate is not sensitivity, and selective verification cannot establish 100% accuracy. Intended-management change does not demonstrate improved survival or prove that routine sequential scanning benefits everyone. The public abstract does not specify the management-questionnaire denominator; percentages are reported as published.[1]
04 · Clinical value
Benefits and limitations
Where fluciclovine may help
- Investigating a specific unresolved question after negative PSMA imaging.
- Assessing local recurrence with relatively low early urinary background.
- Identifying additional sites that could alter radiation planning or further assessment.
What needs caution
- A negative result cannot exclude microscopic recurrence.
- Positive uptake requires clinical and anatomical correlation; biopsy may be needed.
- Inflammation, benign prostate tissue and other tumours can cause uptake.
- Small lesions and some densely sclerotic metastases may be missed.
Detection depends on PSA, tumour biology and scan technique. Additional imaging adds cost and radiation exposure; access depends on local tracer supply and authorisation. This article does not establish Malaysian availability or registration.[3][4]
05 · Clinical reasoning
A practical BCR flowchart
BCR means a PSA rise after treatment intended to cure prostate cancer. The usual definitions differ: after prostatectomy, PSA ≥0.2 ng/mL confirmed on another test; after radiotherapy, PSA ≥2 ng/mL above the nadir. Earlier assessment may be appropriate for a consistent rising PSA.[2][4]
Confirm the PSA trend and clinical context
Review prior treatment, pathology, PSA doubling time, symptoms and whether imaging can change management.
PSMA PET/CT when indicated and available
If unavailable, consider fluciclovine as an alternative according to the clinical question and local access.
Localise and correlate
Multidisciplinary review of disease extent and suitable salvage or systemic options. Investigate uncertain findings when they would change treatment.
Reassess the unresolved question
A negative scan does not prove absence of disease or loss of PSMA expression.
- Possible local recurrence: consider pelvic MRI.
- Selected BCR where another result could alter care: consider fluciclovine.
- Aggressive or discordant progression: consider FDG and tissue assessment when appropriate.
Integrate the result with the patient’s risk and treatment goals
Positive additional imaging: correlate the sites and revise the plan when appropriate. Negative additional imaging: occult disease remains possible. Choose further assessment, surveillance or salvage treatment through multidisciplinary review.
Preserve the opportunity for salvage treatment
For BCR after radical prostatectomy, a negative PET/CT alone should not lead to withholding appropriate salvage prostate-bed radiotherapy. Additional scans should not delay timely treatment. After radiotherapy, suspected local recurrence requires appropriate confirmation before local salvage.[2]
This flowchart is an educational synthesis of references 1–5, not a trial protocol or a rule to scan every patient with all three tracers. MDT means multidisciplinary team; RT means radiotherapy.
Primary sources & professional guidance
References
- Szidonya L, Obrzut S, Lim JY, Latour E, Choudhary G, Hung A, Mallak N. Role of [18F]F-Fluciclovine PET/CT in Patients with Biochemical Recurrence of Prostate Cancer and Negative PSMA PET Results: A Single-Center Study. Journal of Nuclear Medicine. Published online 29 October 2026; jnumed.126.272834. Original article · doi:10.2967/jnumed.126.272834. Prospective study: NCT05722925. Public abstract reviewed; subscription full text was not accessed.
- AUA/ASTRO/SUO. Salvage Therapy for Prostate Cancer Guideline (2024), especially statements 8, 11 and 12. Full guideline · Part I publication.
- Axumin (fluciclovine F 18) prescribing information. Mechanism, indication, biodistribution and interpretation limits. DailyMed product information.
- EANM/SNMMI. [18F]Fluciclovine PET/CT: joint procedure guideline for prostate cancer imaging—version 1.0 (2019). Procedure guideline.
- Fendler WP and colleagues. PSMA PET/CT: joint EANM procedure guideline/SNMMI procedure standard for prostate cancer imaging 2.0 (2023). Procedure standard.
- Calais J, Ceci F, Eiber M and colleagues. 18F-fluciclovine PET-CT and 68Ga-PSMA-11 PET-CT in patients with early biochemical recurrence after prostatectomy: a prospective, single-centre, single-arm, comparative imaging trial. Lancet Oncology. 2019;20:1286–1294. Author manuscript · DOI.
- Fludeoxyglucose F-18 prescribing information. Glucose transport and intracellular phosphorylation by hexokinase. DailyMed FDG product information.
Diagram and evidence notes
The diagram is an original educational schematic. Management-change percentages follow the JNM abstract: 71% overall, 87% after positive scans and 54% after negative scans. Amino acid transport is distinguished from protein synthesis, and urinary activity varies by tracer. The citation uses the verified online publication date and article identifier; a final volume, issue and page range have not been assigned here.
Clinical education. Imaging and treatment decisions require individual assessment by the treating nuclear medicine, urology and oncology teams. This summary does not replace professional judgement.