TROP2 imaging where no tissue test is required
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.
Overview
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.
Neither approved TROP2 antibody-drug conjugate requires a test for TROP2, and no validated blood or tissue assay exists, so when a patient stops responding nobody can tell whether the target has been lost or the payload has failed.
- Neither drug label requires a test, so oncologists have no workflow reason to order a scan and payers have no reason to fund it.
- If the expression-response gradient does not reproduce in the datopotamab deruxtecan datasets, the predictive premise weakens.
- The leading construct is already in a second disease-specific study, so a new entrant starts well behind.
- Any published relationship between TROP2 tracer uptake and antibody-drug conjugate response, which is the missing link in the whole case.
- Whether a quantitative digital-pathology score reaches the breast cancer label, which would make a tissue test the standard and box in the scan.
- Registration of a TROP2 imaging trial outside China, which would be the first sign of industry interest.
The five domains of a radiopharmaceutical due-diligence review, adapted from the Fryback-Thornbury hierarchy of diagnostic efficacy. Each carries the state of the public evidence and the fact behind it, not a score out of five: a single total hides the reason and stops telling candidates apart. Domains marked as carrying most weight are the ones that decide the case at this asset's stage.
TROP2 is widely expressed in breast cancer but with marked intratumoral heterogeneity and discordance between primary and metastatic sites; membranous rather than cytoplasmic localisation appears to matter more than total intensity.
One nanobody tracer has a completed 90-patient feasibility study and a published 73-patient breast-specific study; all of it academic, single-country and not registrational.
No study relates tracer uptake to antibody-drug conjugate response. The comparator's performance is the strongest published signal: ASCENT reported 44% against 22% objective response by TROP2 expression level.
No adverse events reported in the published nanobody cohorts, but no formal dosimetry figure has been published that is worth quoting.
There is no TROP2 companion diagnostic to anchor a claim, and neither drug label requires testing, so an imaging agent would have to define its own indication, most plausibly as an adjunct rather than a selection gate.
Red, amber or green on each review category, each with its reason, so an obvious no-go takes seconds rather than a meeting.
A nanobody construct labelled with gallium-68 already images in humans with same-day kinetics, which is the format this kind of agent needs.
Real heterogeneity and a published expression-response gradient, but both drugs are prescribed today without any test, so the clinical pull is weaker than the biology suggests.
The leading construct is owned by a Chinese biotech and studied with academic partners; no Western clinical programme is disclosed.
Two approved drugs and expanding indications make the addressable population large, but a test that neither label requires has to earn reimbursement on its own evidence.
Gallium-68 on a nanobody; nothing scarce.
The Chinese programme is several years and roughly 160 patients ahead of anyone else.
- Shanghai Novamab with Xiamen and Fudan centresearly clinical
68Ga-MY6349 nanobody PET; completed 90-patient multi-tumour study and a published 73-patient breast-cancer study.
https://www.thno.org/v16p8117.htm - Gileadapproved
Sacituzumab govitecan, approved since 2020 across triple-negative and HR-positive breast cancer; no TROP2 test required.
https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-sacituzumab-govitecan-hziy-metastatic-triple-negative-breast-cancer - Daiichi Sankyo and AstraZenecaapproved
Datopotamab deruxtecan, approved January 2025 for HR-positive disease and later in triple-negative disease; no TROP2 test required.
https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-datopotamab-deruxtecan-dlnk-unresectable-or-metastatic-hr-positive-her2-negative-breast
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