# TROP2 imaging where no tissue test is required

Source: https://nuclide.cc/opportunities/opp-trop2-imaging-heterogeneity/  
Nuclide record `opp-trop2-imaging-heterogeneity` (Opportunity). Data CC BY-NC 4.0, attribute "Data from Nuclide (nuclide.cc)"; commercial use needs a licence.

## TL;DR

Two approved breast cancer drugs work through a protein called TROP2, and neither requires any test for it before use. Tumours vary a lot in how much they carry, and a quarter of patients lose it over time, so nobody currently knows who is being treated for a target that is no longer there.

## Summary

Sacituzumab govitecan and datopotamab deruxtecan are both approved TROP2-directed antibody-drug conjugates, and neither label requires a TROP2 assay. That is not because expression is irrelevant: in the ASCENT biomarker analysis, patients with high TROP2 expression had an objective response rate of 44% against 22% in the low group, with progression-free survival of 6.9 against 2.7 months. It is because the tissue test does not work well enough to gate treatment. A comparison of three immunohistochemistry assays found only fair-to-moderate concordance, there is no validated plasma or ctDNA assay, and a study of circulating tumour cells found no concordance between cell-based and tissue TROP2 status.

Heterogeneity is documented in both space and time: in paired primary and brain-metastasis samples, 21.4% of cases were discordant, and in a longitudinal biopsy series 27.6% of patients showed a marked fall in TROP2 H-score between consecutive time points. Bone metastases showed lower TROP2 than other sites in a post-mortem multi-metastasis study.

The imaging programmes are Chinese, academic and moving quickly. The nanobody tracer 68Ga-MY6349 completed a 90-patient multi-tumour feasibility study and then a 73-patient breast-specific study published in Theranostics in 2026. Nobody has filed anywhere. Because no companion diagnostic exists to be displaced, an imaging agent here would not be competing with an approved assay but filling a space that both drug labels leave open.

## Fields

- Kind: Opportunity
- Last checked: 2026-09-23
- Also known as: TROP2 PET; Trop-2 imaging
- Tags: target crossover; breast; heterogeneity; nanobody

## Sources

- 68Ga-MY6349 in breast cancer, Theranostics 2026: https://www.thno.org/v16p8117.htm
- ASCENT TROP2 biomarker analysis: https://pubmed.ncbi.nlm.nih.gov/34116144/
- TROP2 biomarker review: no companion diagnostic, no validated plasma assay: https://biomarker.onclive.com/breast-cancer/triple-negative-tnbc/biomarkers/trop2
- Longitudinal fall in TROP2 expression during treatment: https://pmc.ncbi.nlm.nih.gov/articles/PMC13379550/
- FDA approval of datopotamab deruxtecan, January 2025: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-datopotamab-deruxtecan-dlnk-unresectable-or-metastatic-hr-positive-her2-negative-breast

## Connected records

- isotopes: [Gallium-68](https://nuclide.cc/isotopes/ga-68/)
- indications: [Triple-negative breast cancer](https://nuclide.cc/indications/breast-triple-negative/)
- technologies: [Immuno-PET](https://nuclide.cc/technologies/immuno-pet/), [PET/CT](https://nuclide.cc/technologies/pet-ct/), [TROP2 PET](https://nuclide.cc/technologies/trop2-pet/)
- targets: [TROP2](https://nuclide.cc/targets/trop2/)

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