In a recent clinical study, researchers demonstrated that imaging with [99mTc]NM-01—a radiolabeled single-domain antibody targeting PD-L1—can predict how patients with advanced non-small cell lung cancer (NSCLC) respond to immunotherapy. This innovative imaging approach offers a promising non-invasive alternative to conventional biopsy-based methods.

The Challenge with Current Biomarkers

PD-L1 expression, typically measured through immunohistochemistry (IHC), is a standard biomarker for determining eligibility for anti-PD-(L)1 therapies like pembrolizumab. However, IHC can be limited by sampling errors, tumor heterogeneity, and invasive procedures—raising the need for more comprehensive, non-invasive diagnostic tools.

Introducing the PECan Study

The PECan study (PD-L1 Expression in Cancer; NCT04436406) set out to explore how [99mTc]NM-01 SPECT/CT imaging correlates with clinical response to pembrolizumab, with or without chemotherapy. [99mTc]NM-01 is a single-domain antibody (also known as a VHH or nanobody) engineered to bind PD-L1 and radiolabeled for imaging.

Fifteen patients with advanced NSCLC underwent both [99mTc]NM-01 SPECT/CT and [18F]FDG PET/CT scans before and after 9 weeks of treatment. PD-L1 expression was also measured by the SP263 IHC assay.

Key Findings

• [99mTc]NM-01 uptake (measured as tumor-to-blood pool ratio) showed moderate correlation with PD-L1 expression from IHC (r = 0.45, p < 0.05).

• Importantly, baseline [99mTc]NM-01 uptake had a stronger correlation with metabolic response on [18F]FDG PET/CT after treatment (r = −0.73, p < 0.05), compared to IHC (r = −0.46, p = 0.06).

• The imaging method also revealed intertumoural heterogeneity in 67% of patients—something that is often missed by biopsy.

Why This Matters

This study underscores the power of single-domain antibodies in diagnostic imaging. Their small size, high specificity, and rapid clearance make them ideal for SPECT/CT applications. With [99mTc]NM-01, clinicians can visualize PD-L1 expression across both primary and metastatic sites—non-invasively and in real time.

What It Means for the Future

The success of [99mTc]NM-01 in predicting early treatment response marks a significant step forward in precision oncology. It also highlights the growing impact of VHH-based technologies beyond therapeutics—into imaging, diagnostics, and clinical decision-making.

At AlpalifeBio, we’re proud to support innovation in single-domain antibody discovery and development. We believe technologies like [99mTc]NM-01 are paving the way for smarter, more personalized cancer care.

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Reference: Nature