# HER3 imaging, and why three tracers stalled

Source: https://nuclide.cc/opportunities/opp-her3-imaging-crossover/  
Nuclide record `opp-her3-imaging-crossover` (Opportunity). Data CC BY-NC 4.0, attribute "Data from Nuclide (nuclide.cc)"; commercial use needs a licence.

## TL;DR

HER3 sits on most lung cancers and there are drugs aimed at it, so a scan showing which tumours carry it looks obvious. Three attempts were made and all three stopped, largely because the drug's own trials could not show that how much HER3 a tumour has predicts whether the drug works.

## Summary

HER3 is the textbook crossover case: expressed in around 80% of non-small cell lung cancers, targeted by patritumab deruxtecan and other antibody-drug conjugates, with no radioligand in routine use. Three antibody PET tracers were built (64Cu-patritumab, 89Zr-GSK2849330, 89Zr-lumretuzumab) and all three belong to drug programmes that lost momentum or were discontinued. Only one HER3 imaging trial is currently recruiting: 89Zr-patritumab deruxtecan at the Netherlands Cancer Institute with Daiichi Sankyo as collaborator, 16 patients, on the explicit rationale that HER3 expression can be assessed non-invasively including at sites that are difficult to biopsy.

The honest problem is not the tracer. Patritumab deruxtecan's own biomarker analyses report no relationship between efficacy and HER3 protein expression by immunohistochemistry, and the SOLTI TOT-HER3 work found activity across a wide range of ERBB3 mRNA and HER3 protein levels, suggesting limited predictive value. One published tracer study could determine no correlation between tumour uptake and ex-vivo immunohistochemistry. The drug itself received a complete response letter in June 2024 on a third-party manufacturing finding, and the BLA was withdrawn in May 2025 after HERTHENA-Lung02 missed its overall survival endpoint.

This record exists as a worked negative: the crossover lens will keep producing targets like this, and the discipline it needs is to ask whether expression predicts benefit before assuming a companion diagnostic has a market.

## Fields

- Kind: Opportunity
- Last checked: 2026-09-23
- Also known as: HER3 PET
- Tags: target crossover; worked negative; lung; companion diagnostic

## Sources

- NCT06222489: 89Zr-patritumab deruxtecan PET/CT: https://clinicaltrials.gov/study/NCT06222489
- No relationship between HER3-DXd efficacy and HER3 immunohistochemistry, Nature Communications 2024: https://www.nature.com/articles/s41467-024-50056-y
- Complete response letter for patritumab deruxtecan, June 2024: https://daiichisankyo.us/press-releases/-/article/patritumab-deruxtecan-bla-submission-receives-complete-response-letter-from-fda-due-to-inspection-findings-at-third-party-manufacturer
- No validated HER3 immunohistochemistry assays or thresholds (review): https://pmc.ncbi.nlm.nih.gov/articles/PMC12758208/
- Fluoroestradiol F-18 label, the receptor-imaging precedent: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/212155s000lbl.pdf

## Connected records

- isotopes: [Copper-64](https://nuclide.cc/isotopes/cu-64/), [Zirconium-89](https://nuclide.cc/isotopes/zr-89/)
- indications: [Non-small cell lung cancer](https://nuclide.cc/indications/nsclc/)
- technologies: [Immuno-PET](https://nuclide.cc/technologies/immuno-pet/), [PET/CT](https://nuclide.cc/technologies/pet-ct/)
- targets: [HER3 (ERBB3)](https://nuclide.cc/targets/her3/)

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