[18F]AIF-NOTA-PCP2 Shows PD-L1 Monitoring Potential in Head and Neck Cancer

[18F]AIF-NOTA-PCP2 uptake changes reflected therapeutic response to pembrolizumab (Keytruda) plus chemotherapy in a small cohort of patients with PD-L1–positive head and neck squamous cell carcinoma (HNSCC).

[18F]AIF-NOTA-PCP2 may be a safe and effective PET tracer for noninvasive PD-L1 evaluation in patients with head and neck cancers, according to results from a prospective trial (NCT06690216) presented at the 2025 Society of Nuclear Medicine and Molecular Imaging Annual Meeting.

Results revealed that [18F]AIF-NOTA-PCP2 showed acceptable dosimetry among all patients with head and neck cancers (n = 24) assessed with the tool. Additionally, no tracer-related adverse effects were observed in the study. Regarding biodistribution, the highest uptake was noted in the spleen, with minimal off-target uptake in the liver and intestines, as well as low renal uptake.

High PD-L1 expression, characterized as having a tumor positive score (TPS) of 20% or greater, was associated with a significantly higher maximum standardized uptake value (SUVmax) at 5.92 vs 2.39 in tumors with a TPS of less than 20% (P <.001). Additionally, a strong positive correlation was observed between SUVmax and PD-L1 TPS, with a Spearman’s rank correlation of 0.890 (P <.001); the SUVmean vs PD-L1 TPS rs was 0.837 (P <.001).

Additionally, variation in uptake was observed based on anatomical site, with higher uptake observed in orbital fibrous, tonsil, and oropharynx tumors, and lower uptake observed in larynx and oral cavity lesions. Furthermore, nonsquamous histology was associated with a higher uptake than squamous histology, with respective SUVmaxof 6.22 vs 3.61 (P = .041). HPV positivity in the HNSCC was also associated with higher SUVmax; at 5.93 vs 2.25 (P = .007).

[18F]AIF-NOTA-PCP2 uptake changes reflected therapeutic response to pembrolizumab (Keytruda) plus chemotherapy in a small cohort of patients with PD-L1–positive head and neck squamous cell carcinoma (HNSCC). Among 3 patients with HNSCC who responded to treatment with pembrolizumab and chemotherapy, PD-L1 downregulation was observed in all patients.

Specifically, in 1 patient who experienced a complete response, a rapid decrease in SUVmax was observed, from 6.52 to 4.06, a 37.7% decrease 1 week following therapy. Among 2 patients who experienced a partial response, a significant decrease in SUVmax was observed following 3 cycles of study regimen, with 54.0% and 23.0% decreases in each patient, respectively.

“[With] [18F]AIF-NOTA-PCP2 … uptake changes clearly reflected therapeutic response. Responders showed significant and early decreases in PD-L1 downregulation.” Yong Wang, MD, managing director of Shandong Cancer Hospital and Institute in Jinan, Shandong, China, said in an oral presentation of the data. “[By] contrast, nonresponders showed a stable or increased uptake, [showing] strong potential for [18F]AIF-NOTA-PCP2 [in] early, dynamic PD-L1 monitoring.”

Patients with HNC who were immunotherapy-naive across diverse tumor subsites were assessed with the peptide-based PET tracer. The median age of enrolled patients was 59.5 years, 79.2% of patients were males, and 25% were HPV positive. A total of 24 patients underwent [18F]AIF-NOTA-PCP2 PET/CT scans,17 underwent paired [18F]FDG PET/CT scans, and a total of 5 patients underwent immunotherapy monitoring.

Preclinical data showed that [18F]AIF-NOTA-PCP2 had an excellent profile, with a high PD-L1 affinity. The half-maximal inhibitory concentration (IC50) of the tracer was 24.7 nanomolars (nM). Additionally, selective targeting of PD-L1–positive tumors in xenograft models were observed in preclinical trials.

A head-to-head comparison assessing [18F]FDG PET/CT scans showed limited concordance between the 2 tracers. A weak correlation was observed between each (P = .042), with many FDG-avid tumors showing low PCP2 uptake and vice versa.

In conclusion, Wang noted that future perspectives should include validation in larger, multicenter cohorts of patients with head and neck cancer, applications of [18F]AIF-NOTA-PCP2 in other cancer types, and the development of standardized immune-PET response criteria.

Reference

Wang Y, Liu Z, Yu J, Hu M, et al. Can [18F]FDG-PET/CT predict PD-L1 expression in head and neck carcinoma? A head-to-head comparison with a novel PD-L1 PET tracer. Presented at: 2025 Society for Nuclear Medicine and Medical Imaging Meeting; June 21-24, 2025; New Orleans, LA.