[18F]AlF-NOTA-PCP2 PET/CT to Assess PD-L1 Status in Head and Neck Cancer: Head-to-Head Comparison With [18F]FDG...

Area of Science:

• Oncology
• Radiochemistry
• Molecular Imaging

Background:

• PD-L1 expression heterogeneity in biopsies limits treatment prediction in head and neck cancer (HNC).
• Molecular imaging offers a dynamic, non-invasive alternative to assess PD-L1 expression.
• Development of targeted radiotracers is crucial for personalized cancer therapy.

Purpose of the Study:

• To develop and evaluate [18F]AlF-NOTA-PCP2, a novel PET tracer targeting PD-L1.
• To compare the clinical utility of [18F]AlF-NOTA-PCP2 PET/CT with [18F]FDG PET/CT in HNC patients.
• To assess the tracer's ability to monitor dynamic changes in PD-L1 expression during immunotherapy.

Main Methods:

• Preclinical validation in HNC xenografts using competitive binding assays and micro-PET/CT.
• Prospective clinical trial enrolling 24 HNC patients for [18F]AlF-NOTA-PCP2 PET/CT scans.
• Paired [18F]FDG PET/CT scans in 17 patients; PD-L1 quantification via 22C3 immunohistochemistry (IHC).

Main Results:

• [18F]AlF-NOTA-PCP2 demonstrated high PD-L1 affinity and selective tumor targeting in preclinical models.
• Tracer uptake strongly correlated with PD-L1 tumor proportion score (TPS) in HNC patients (rs = 0.890, P < 0.001).
• Limited concordance between [18F]AlF-NOTA-PCP2 and [18F]FDG SUVmax (rs = 0.323, P = 0.042); uptake varied by HPV status and tumor site.

Conclusions:

• [18F]AlF-NOTA-PCP2 PET/CT is a superior, non-invasive method for assessing PD-L1 expression in HNC.
• The tracer's specificity and favorable biodistribution make it valuable for monitoring immunotherapy.
• This molecular imaging approach can inform treatment decisions in HNC management.