There's a growing recognition that the molecular profile of a primary tumor can differ significantly from its metastases. To guide treatment more accurately, the preferred practice is to biopsy an accessible metastatic lesion when possible, as this better reflects the biology of the active disease being treated.

ctDNA testing (liquid biopsy) is more effective than tissue biopsy for identifying ESR1 mutations. It samples DNA from all metastatic sites, capturing the disease's genetic heterogeneity and reflecting the most active resistance mechanisms, unlike a single-site needle biopsy which can miss them.

In cases of suspected glioma recurrence post-radiation, FET PET imaging can provide a more accurate diagnosis than MRI perfusion, even when MRI findings suggest tumor growth. This allows clinicians to avoid unnecessary changes in therapy based on potentially misleading MRI data.

There is a growing suspicion that conventional imaging understages many presumed early-stage lobular cancers. Using FES PET-CT upfront could detect small-volume metastatic disease missed by other methods. This would reclassify patients to a metastatic setting, sparing them the morbidity of major local surgeries that would not be curative.

FES PET-CT relies on a tracer binding to estrogen receptors. If a patient is on ER modulators or down-regulators (like tamoxifen or fulvestrant), these drugs will block the tracer, causing a false-negative scan. Clinicians must plan for a washout period of several weeks before imaging, which requires careful treatment coordination.

While powerful, FES PET-CT is a specialized tool with key limitations. It is not effective for evaluating disease in the liver, a common site of breast cancer metastasis. Furthermore, it cannot detect any disease that has become estrogen receptor-negative. Therefore, it must be used as part of a broader imaging program, not as a standalone surveillance tool.

Fibrogen uses its PET imaging agent in Phase 2 not to pre-select patients, but to correlate target expression with treatment response. This data will allow them to enrich their Phase 3 trial with patients most likely to respond, significantly increasing the probability of success.

A biopsy can confirm ER-positive tissue, but FES PET-CT demonstrates that these receptors are functional and capable of binding. This distinction is critical, as some tumors may have non-functional receptors or heterogeneous expression. A positive FES scan provides strong evidence that a patient is a good candidate for endocrine therapy.

The introduction of highly sensitive PSMA PET scans means established endpoints like Metastasis-Free Survival (MFS) may no longer be valid. A metastasis detected by PET likely has a different, better prognosis than one found with older imaging, requiring new validation for this key endpoint.