# DLL3 imaging for small-cell lung cancer

Source: https://nuclide.cc/opportunities/opp-dll3-imaging-sclc/  
Nuclide record `opp-dll3-imaging-sclc` (Opportunity). Data CC BY-NC 4.0, attribute "Data from Nuclide (nuclide.cc)"; commercial use needs a licence.

## TL;DR

A drug that attacks small-cell lung cancer through a protein called DLL3 is already approved, but there is no approved scan that shows whether a patient's tumours still carry that protein. Doctors decide from a single biopsy taken from one place, which cannot show what the rest of the disease is doing.

## Summary

Tarlatamab, a DLL3-directed bispecific T-cell engager, received accelerated FDA approval on 16 May 2024 and traditional approval on 19 November 2025, and DLL3-directed antibody-drug conjugates, CAR-T cells and a second T-cell engager (obrixtamig) are in trials. Patient selection rests on tissue immunohistochemistry from one archival or fresh biopsy. DLL3 is expressed in 85% of small-cell lung cancers at a 25% cut-off in the largest real-world series (895 of 1,050 patients), so most patients qualify on a single sample, but nothing in routine practice shows whether every metastatic site still expresses the target.

One imaging agent has human data. The zirconium-89-labelled anti-DLL3 antibody 89Zr-DFO-SC16.56, run investigator-initiated at Memorial Sloan Kettering under NCT04199741, was reported in Lancet Oncology in 2024: 18 patients, DLL3-avid tumours delineated on a single scan in 12 of 15 patients in the expansion cohort, uptake congruent with DLL3 immunohistochemistry in 15 of 16 patients with evaluable tissue, mean effective dose 0.49 mSv/MBq, one grade 1 allergic reaction and no grade 2 or worse adverse events. The trial is still recruiting with an estimated 105 patients. A gallium-68 DLL3 tracer opened in China in May 2026 (NCT07677787, 20 patients planned) and has not reported. A next-generation MSK construct, 89Zr-DFO-TDI-Y-010, with a lutetium-177 therapeutic pair, is preclinical.

The gap is therefore not biological plausibility, which a published 94% concordance with immunohistochemistry supports, but the absence of any industry-sponsored development path: the only clinical agent is an academic antibody with multi-day imaging kinetics, and no DLL3 imaging agent has been filed with any regulator.

## Fields

- Kind: Opportunity
- Last checked: 2026-09-23
- Also known as: DLL3 PET; delta-like ligand 3 imaging
- Tags: theranostic gap; companion diagnostic; lung; neuroendocrine

## Sources

- First-in-human DLL3 immuno-PET, Lancet Oncology 2024: https://pubmed.ncbi.nlm.nih.gov/38950555/
- NCT04199741: 89Zr-DFO-SC16.56 immuno-PET of neuroendocrine tumours: https://clinicaltrials.gov/study/NCT04199741
- NCT07677787: DLL3-targeted PET/CT in small-cell lung cancer (gallium-68): https://clinicaltrials.gov/study/NCT07677787
- DLL3 expression in 1,050 patients, Lung Cancer 2020: https://pubmed.ncbi.nlm.nih.gov/32745892/
- FDA: accelerated approval of tarlatamab, May 2024: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-tarlatamab-extensive-stage-small-cell-lung-cancer

## Connected records

- isotopes: [Gallium-68](https://nuclide.cc/isotopes/ga-68/), [Lutetium-177](https://nuclide.cc/isotopes/lu-177/), [Zirconium-89](https://nuclide.cc/isotopes/zr-89/)
- indications: [Small-cell lung cancer](https://nuclide.cc/indications/sclc/)
- technologies: [Immuno-PET](https://nuclide.cc/technologies/immuno-pet/), [PET/CT](https://nuclide.cc/technologies/pet-ct/)
- targets: [DLL3](https://nuclide.cc/targets/dll3/)

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