Overview

This Phase I, single-institution, open-label study will evaluate the safety, tolerability, and diagnostic performance of \[18F\]NOTA-ABY030 PET/CT in patients with head and neck squamous cell carcinoma (HNSCC) who present with indeterminate lesions on standard imaging. The investigational agent is a radiolabeled anti-EGFR affibody designed for rapid clearance and improved tumor-to-background contrast. All participants will receive a 50 mg cetuximab loading dose followed by a bolus of \[18F\]NOTA-ABY030, with PET/CT imaging performed at defined intervals to assess biodistribution and lesion uptake. The primary objective is to determine safety and tolerability; secondary objectives include radiation dosimetry and comparison of sensitivity and specificity to conventional imaging modalities (MRI, CT, and \[18F\]FDG-PET/CT). This approach aims to improve diagnostic accuracy, reduce unnecessary biopsies, and streamline treatment decisions for patients with HNSCC.

Eligibility

Inclusion Criteria:

1. Age ≥ 18 years.
2. Subjects diagnosed with any T stage, any subsite within the head and neck. Subjects with recurrent disease or a new primary will be allowed.
3. Must have evidence of indeterminate metastatic and/or primary SCC based on clinical imaging or Primary SCC with suspicious Lymph Nodes standard image modalities prior to surgical removal
4. Have acceptable lab values, including the following clinical results (if values are considered clinically significant per investigator, participants must be asymptomatic):
   1. Hemoglobin ≥ 9gm/dL
   2. White blood cell count \> 3000/mm3
   3. Platelet count ≥ 100,000/mm3
   4. Serum creatinine ≤ 1.5 times upper reference range
   5. Potassium
   6. Magnesium
   7. Phosphorus

Exclusion Criteria:

1. Myocardial infarction (MI); cerebrovascular accident (CVA); uncontrolled congestive heart failure (CHF); significant liver disease; or unstable angina within 6 months prior to enrollment.
2. Prior severe infusion reactions or hypersensitivity to other monoclonal antibody therapies.
3. Pregnant (based on Screening serum or urine pregnancy test administered before infusions), or breastfeeding.
4. Participants with known hypersensitivity to NOTA-ABY-030, cetuximab, murine, or any of the drug components used in this trial.
5. Subjects with history or evidence of interstitial pneumonitis or pulmonary fibrosis.
6. Severe renal disease or anuria.
7. Participants presenting with a baseline QTcF interval \> than 480 milliseconds.
8. Those with an allergy to red meat, a history of tick bites, and alpha-gal syndrome will be given extra consideration.