# A liver-cleared Nectin-4 tracer for urothelial cancer

Source: https://nuclide.cc/opportunities/opp-nectin4-imaging-urothelial/  
Nuclide record `opp-nectin4-imaging-urothelial` (Opportunity). Data CC BY-NC 4.0, attribute "Data from Nuclide (nuclide.cc)"; commercial use needs a licence.

## TL;DR

An approved bladder cancer drug works by latching onto a protein called Nectin-4, and half of patients lose that protein as the disease spreads. The one scan built to show it is cleared through the kidneys, so the bladder and the nearby lymph nodes glow with waste tracer and are the hardest places to read.

## Summary

Enfortumab vedotin, a Nectin-4-directed antibody-drug conjugate, has been approved since December 2019 and now reaches into the perioperative setting: in November 2025 the FDA approved pembrolizumab with enfortumab vedotin as neoadjuvant then adjuvant treatment for cisplatin-ineligible muscle-invasive bladder cancer, on a trial of 344 patients that reported a hazard ratio of 0.40 for recurrence, progression or death. Selection does not require a Nectin-4 assay, yet Nectin-4 expression falls in more than half of cases during metastatic progression and more than a third of metastases are Nectin-4-negative.

The imaging work is almost entirely Chinese and academic. The bicyclic peptide tracer 68Ga-N188, from Peking University, has a published first-in-human study in 14 patients with advanced urothelial cancer plus two healthy volunteers, and a 62-patient head-to-head study against FDG across 16 tumour types. It is registered in three Chinese trials. Its published limitation is decisive for the indication that matters most: the tracer is excreted in urine, and a 2025 review states plainly that this poses challenges for in-situ bladder cancer detection because of high background activity in the urinary tract.

So the opportunity is not a target in search of a tracer, nor a tracer in search of a target, but a pharmacokinetic specification: a Nectin-4 ligand cleared hepatobiliary rather than renally, which could read the bladder wall and the pelvic nodes where staging and surgical decisions are actually made.

## Fields

- Kind: Opportunity
- Last checked: 2026-09-23
- Also known as: Nectin-4 PET; nectin-4 imaging
- Tags: theranostic gap; bladder; clearance; pelvic staging

## Sources

- 68Ga-N188 first-in-human, Clinical Cancer Research 2023: https://pubmed.ncbi.nlm.nih.gov/37093191/
- 68Ga-N188 against FDG in 62 patients, Journal of Nuclear Medicine 2024: https://pubmed.ncbi.nlm.nih.gov/38719240/
- Review noting urinary excretion as a barrier to in-situ bladder detection, 2025: https://pmc.ncbi.nlm.nih.gov/articles/PMC12227459/
- Nectin-4 expression and loss in metastatic progression, Clinical Cancer Research 2023: https://aacrjournals.org/clincancerres/article/29/8/1496/725070/Membranous-NECTIN-4-Expression-Frequently
- FDA: perioperative enfortumab vedotin plus pembrolizumab, November 2025: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-enfortumab-vedotin-ejfv-muscle-invasive-bladder-cancer

## Connected records

- isotopes: [Fluorine-18](https://nuclide.cc/isotopes/f-18/), [Gallium-68](https://nuclide.cc/isotopes/ga-68/)
- indications: [Urothelial cancer](https://nuclide.cc/indications/urothelial-cancer/)
- technologies: [Peptide-drug & small-molecule-drug conjugates](https://nuclide.cc/technologies/peptide-drug-conjugate/), [PET/CT](https://nuclide.cc/technologies/pet-ct/)
- targets: [Nectin-4](https://nuclide.cc/targets/nectin4/)

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