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Table 2 Targets in the tumor microenvironment and targeted imaging agents in HNSCC

From: Advances in nuclear medicine-based molecular imaging in head and neck squamous cell carcinoma

Targets

Targeted Imaging Agents

Tumor staging

Results

Imaging Technique

Refs.

CAFs

68Ga-FAPI

Primary tumor

No diet or fasting is required before 68Ga-FAPI examination, and image acquisition can be started right after tracer injection

PET/CT

[73]

SHOWS a much higher mean TBRmax than FDG, making it easier to differentiate tumors from inflammation

PET/CT

[74]

68Ga-FAPI and 18F-FDG shows equivalent and high SUL uptake values within the primary site of OSCC

PET/CT

[75]

Has advantages over 18F-FDG PET/CT in assessing skull base invasion and cavernous sinus involvement in NPC patient

PET/CT

[76]

Improves the detection rate of primary tumor in FDG negative HNCUP patients

PET/CT

[77]

Serves as a novel approach for planning of image-guided radiotherapy

PET/CT

[78]

As a potential complement to MRI for T-staging and radiotherapy planning in NPC patients

PET/CT

[79]

Locoregional and distant metastases

68Ga-FAPI has improved specificity compared to18F-FDG, potentially preventing overtreatment caused by false-positive cervical lymph nodes-indicated neck dissections

PET/CT

[80]

68Ga-FAPI has higher specificity and accuracy than 18F-FDG for evaluating OSCC neck lymph node metastases, especially for N0 neck status

PET/CT

[81]

Superior sensitivity to18F-FDG PET/CT for detecting lymph node, bone and visceral metastases

PET/CT

[82]

68Ga-FAPI PET/MR has the potential to serve as a single-step staging modality for NPC patients with suspected distant metastases

PET/MR

[83]

PD-1/PD-L1

89Zr-DFO-durvalumab

Clinical

The first PD-L1 PET/CT study in patients with recurrent or metastatic HNSCC, showing feasibility and safety

PET/CT

[98]

89Zr-PD-L1 mAb

Preclinical

Potentially valuable for assessing radiation-induced PD-L1 upregulation in HNC and melanoma

PET/CT

[101]

  1. 18F-FDG Fluorine-18 Fluorodeoxyglucose, 68Ga Gallium-68, 89Zr Zirconium-89, CAFs  cancer-associated fibroblasts, CT computed tomography, FAPI fibroblast activation protein-targeting inhibitor, HNC head and neck cancer, HNCUP head and neck cancer of unknown primary, MR magnetic resonance, MRI magnetic resonance imaging, NPC nasopharyngeal carcinoma, OSCC oral squamous cell carcinoma, PD-1 programmed cell death protein-1, PD-L1 programmed cell death-ligand 1, PET positron emission tomography, SUL standardized uptake value normalized by lean body mass, TBR tumor-to-background ratio