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What the Review Reports

Schäfer et al. (RWTH Aachen/Maastricht) synthesize the last 2–3 years of PET/SPECT radiotracer development in breast cancer, organizing targets into tumor-cell markers (glucose metabolism, ER, PR, HER2, GRPR, PARP, hypoxia, CXCR4, PD-L1, TROP2, IGF-1R) and tumor-microenvironment targets (FAP on CAFs, PSMA on tumor vasculature, TSPO on macrophages) Radiotracer target taxonomy.

Key quantitative claims: ER is expressed in 70–80% of BCa; GRPR is overexpressed in 76% of primary BCa and 83% of ER-positive tumors; PSMA is present on 74% of BCa tumor vasculature; TNBC comprises ~15% of cases. Reported trial data include [18F]F-4FMFES achieving better tumor contrast and lower false-negative rates than [18F]FES (NCT04824014); [68Ga]Ga-NOTA-MVK-ZHER2:2891 SUVmax of 9.4–21 in HER2-positive vs 2.7–6.2 in HER2-negative lesions; and [68Ga]Ga-FAPI-46 detecting axillary metastases more frequently than FDG Quantitative trial results in review.

Critical Assessment

Strengths: the review is current (2025), references 154 works, integrates a trial-number table, and candidly lists limitations (FES liver background uptake, washout periods of 8–28 weeks with ER antagonists, FMISO slow clearance, GRPR physiological breast uptake). It also correctly notes IHC may misclassify hormone receptor status in up to 20% of tests globally — a key motivating rationale for FES imaging. Weaknesses: it is a narrative (not systematic) review with no PRISMA methodology, cited cohorts are very small (NeoFIND n=19 with 5 BCa; Cu-SAR-BBN n=7; Pentixafor studies n=7–30), several claims rest on unpublished or conference data, and the HER2 section has an apparent garbled sentence ("lobular BCa and showed better results compared to FAPI" in the FAPI subsection) suggesting production errors. Many trials cited have no published results, so claims about their promise are speculative. No cost-effectiveness, dosimetry comparison across tracers, or discussion of overdiagnosis is provided.

Evidence Confidence and What Would Change It

The central conclusion — that HR-positive imaging is clinically validated while TNBC imaging remains investigational — is well-supported by the trial landscape mapped in the review and is consistent with guideline documents it cites (EANM/SNMMI FDG and FES guidelines). Confidence is moderate: the underlying trials are heterogeneous and underpowered, and radiotracer performance claims (e.g., F-4FMFES superiority) come from preliminary phase II results not yet fully published. The conclusion would be falsified if adequately powered prospective studies showed FES uptake fails to predict endocrine therapy response, or if FAPI/GRPR imaging shows no staging advantage over FDG in blinded multicenter trials Clinical maturity gradient across targets.

Best Evidence: FES vs IHCGraph TNBC Tracer LandscapeTest FAPI vs FDG Hypothesis

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Author Review: Laura SchäferAuthor Review: Betül AltunayAuthor Review: Amelie HeeschAuthor Review: Thiemo Van NijnattenAuthor Review: Sofia VazAuthor Review: Malik Eid JuweidAuthor Review: Felix Manuel Mottaghy

 BGPT Paper Review

Study Novelty

Well-timed 2025 synthesis of a fast-moving tracer field, but reviews earlier work exist; incremental rather than groundbreaking.

Scientific Quality

Narrative review with candid limitations and a useful trial table, but no systematic methodology, small cited cohorts, reliance on unpublished trial data, and at least one garbled sentence (e.g., in the FAPI section) indicating editorial lapses.

Study Generality

Covers the full breadth of BCa subtypes and targets, useful broadly, but confined to nuclear imaging rather than general oncology.

Study Usefulness

A useful current roadmap for nuclear medicine clinicians and trial designers; the NCT registry mapping adds practical value.

Study Reproducibility

As a narrative review there is no reproducible methodology; trial numbers allow independent verification but the literature selection process is opaque.

Explanatory Depth

Covers tracer biology reasonably but mostly at descriptive level; mechanisms of tracer uptake variability and heterogeneity are noted without quantitative depth.