VM4-037
Source VM4-037 at Peptiology
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Summary
VM4-037 is a small‑molecule radiotracer labelled with fluorine‑18 (^18F‑VM4-037) designed for positron emission tomography (PET) imaging of carbonic anhydrase IX (CA‑IX), a protein over‑expressed in hypoxic tumours and clear‑cell renal cell carcinoma (ccRCC). The compound is investigated as a non‑invasive marker of CA‑IX expression and tumour hypoxia, primarily for detecting metastatic disease and for research into CA‑IX‑targeted theranostics.
Mechanism of Action
The tracer incorporates a sulfonamide moiety that binds the zinc‑containing active site of CA‑IX, inhibiting its enzymatic activity. Upon intravenous injection, the ^18F label emits positrons detectable by PET. Tissue regions with high CA‑IX density retain the tracer longer than surrounding normal tissue, allowing image contrast that reflects CA‑IX expression and, indirectly, hypoxic micro‑environments.
What the Research Shows
Four peer‑reviewed studies provide the current evidence base. A 2014 human biodistribution study in four healthy volunteers showed very high liver and kidney uptake, with an estimated effective radiation dose of about 10 mSv for a typical 370 MBq injection, deeming the dose safe but limiting imaging of CA‑IX in those organs. Preclinical work in 2015 using two CA‑IX‑positive tumour models demonstrated that tumour uptake was comparable to background, questioning specificity. A 2016 phase‑II pilot in eleven patients with renal masses found the tracer well tolerated, with primary kidney lesions difficult to visualise due to high normal kidney activity, yet metastatic lesions were clearly detected, showing moderate SUV values (~3). A 2026 literature review lists ^18F‑VM4‑037 among promising CA‑IX agents but notes the need for structural optimisation to improve selectivity and reduce off‑target organ exposure.
Reported Benefits
VM4‑037 enables same‑day PET imaging of CA‑IX expression without requiring invasive biopsies, offering a functional read‑out of tumour hypoxia. Clinical pilot data suggest it can reliably highlight metastatic ccRCC lesions, potentially aiding staging and treatment planning. The radiotracer is well tolerated, with no reported adverse events in the human studies conducted to date.
Limitations of the Evidence
High non‑specific accumulation in liver and kidneys reduces contrast for primary renal tumours, making lesion detection challenging in the kidney. Preclinical models showed limited tumour‑specific uptake, and overall tumour SUV values are modest. Evidence is limited to small cohorts and early‑phase studies; larger trials are lacking, and the tracer’s performance compared with newer CA‑IX agents remains unestablished.
Safety Considerations
No acute adverse events were reported in the human studies. Radiation exposure from a standard 370 MBq dose results in an effective dose of roughly 10 mSv, which is within accepted diagnostic limits, but the kidneys and liver receive the highest absorbed doses (~101 mGy and 89 mGy respectively). Caution is warranted regarding cumulative radiation exposure, especially in repeated imaging protocols.
How It Is Administered
VM4‑037 is administered intravenously as an ^18F‑labelled solution. In clinical protocols, imaging is typically performed at about 60 minutes post‑injection, with some dynamic scans acquired during the first 45 minutes. The administered activity in published studies has been around 370 MBq, but exact dosing is determined by the imaging facility and regulatory guidelines.
Routes of Administration
No administration routes recorded yet.
Goals & Uses
No goal associations recorded yet.
Contraindications
No contraindications recorded yet.
Adverse Effects
No adverse effects recorded yet.
Drug Interactions
No drug interactions recorded yet.
Population Constraints
No population constraints recorded yet.
Regulatory Status
No regulatory status recorded yet.
Evidence & Sources
- Journal ArticleModerateDoss M, et al.2014-01-01T00:00:00.000000Z
- Journal ArticleLowPeeters SG, et al.2015-01-01T00:00:00.000000Z
- Journal ArticleLowTurkbey B, et al.2016-01-01T00:00:00.000000Z
- Journal ArticleModerateLiu Y, et al.2026-01-01T00:00:00.000000Z
Frequently Asked Questions
What does VM4‑037 detect?
VM4‑037 binds to carbonic anhydrase IX, a protein that is over‑expressed in hypoxic tumour cells, especially in clear‑cell renal cell carcinoma. PET imaging therefore reflects the spatial distribution of CA‑IX expression.
Is VM4‑037 safe for patients?
In the small human studies reported, the tracer caused no adverse events. The radiation dose from a typical injection (~10 mSv effective dose) is comparable to other diagnostic PET scans, though kidneys and liver receive higher absorbed doses.
Can VM4‑037 reliably image primary kidney tumours?
Primary renal lesions are difficult to visualise because normal kidney tissue shows high background uptake. The tracer is more useful for detecting metastatic lesions where background activity is lower.
How does VM4‑037 compare to newer CA‑IX tracers?
A recent review cites VM4‑037 as promising but notes that newer agents (e.g., ^68Ga‑NY104, ^64Cu‑PD‑32766) may offer higher specificity and lower off‑target organ uptake. Direct comparative data are not yet available.
What imaging protocol is used with VM4‑037?
Patients receive an intravenous injection of the ^18F‑labelled tracer, followed by whole‑body PET/CT imaging at about one hour post‑injection. Some studies also acquire dynamic scans during the first 45 minutes to assess tracer kinetics.
What is VM4-037?
VM4-037 is a small‑molecule radiotracer labelled with fluorine‑18 (^18F‑VM4-037) designed for positron emission tomography (PET) imaging of carbonic anhydrase IX (CA‑IX), a protein over‑expressed in hypoxic tumours and clear‑cell renal cell carcinoma (ccRCC). The compound is investigated as a non‑invasive marker of CA‑IX expression and tumour hypoxia, primarily for detecting metastatic disease and for research into CA‑IX‑targeted theranostics.