Table 1.

Targets on the tumor cell and targeted imaging agents in HNSCC

Targets	Targeted Imaging Agents	Type of Molecule	Results	Imaging Technique	Refs.
EGFR	111In-Cetuximab	mAb	Optimally dosed 111In-Cetuximab accumulate effectively in HNSCC xenografts, suggesting the imaging uptake can reflect the actual EGFR expression of the tumor	SPECT	[16]
	111In-Cetuximab-F(ab')2	Fab fragment	Distinguishes HNSCC xenografts with differential EGFR expression, and monitors therapy response of radiotherapy and/or cetuximab treatment	SPECT	[17–19]
	64Cu-Cetuximab-F(ab')2	Fab fragment	64Cu-Cetuximab-F(ab')2 uptake correlates with EGFR expression in HNSCC xenografts	PET/CT	[20]
	89Zr-Cetuximab	mAb	Suggests a safe imaging dosing of 60 MBq and a minimum scan interval of 6 days	PET/CT	[21]
	89Zr-Cetuximab	mAb	Provides additional information about EGFR drug accessibility	PET/CT	[22]
	89Zr-DFO-Cetuximab	mAb	Allows to monitor drug resistance in HNSCC patients during cetuximab treatment	PET/CT	[23]
	18F-FBEM-EGF	peptide	Bocking liver uptake of targeting agents using optimized unlabeled EGF ligands increase the tumor-to-liver ratio	PET/CT	[24]
	89Zr/18F-ZEGFR:03115	Affibody	Assessment of different levels of EGFR in vivo and changes in EGFR expression in response to cetuximab	PET/CT	[25]
	64Cu-DOTA-Panitumumab	mAb	EGFR expression in HNSCC xenograft does not correlate with the uptake of 64Cu-DOTA-Panitumumab	PET/CT	[26]
	64Cu-/177Lu-PCTA-Cetuximab	mAb	Has potential for target selection using immuno-PET imaging and RIT-targeted therapy in cetuximab-resistant HNSCC tumors expressing EGFR	PET/CT	[27]
	64Cu/177Lu-DOTA-Panitumumab F(ab')2	Fab fragment	Suggests the feasibility of predicting the radiation equivalent doses to HNSCC and normal organs	PET/CT	[28]
CD44v6	89Zr-cmAb U36	mAb	Immuno-PET using 89Zr-cmAb U36 performs at least as well as CT/MRI for detection of lymph node metastases	PET/CT	[32]
	99mTc/186Re-cmAb U36	mAb	The pharmacokinetics of 186Re-cMAb U36 can be predicted by 99mTc-cMAb U36	SPECT	[33]
	99mTc-BIWA 1	mAb	BIWA 1 shows high selective tumor uptake, but it is immunogenic and exhibits heterogeneous aggregation	SPECT	[35]
	99mTc-BIWA 4	mAb	Safely used in HNSCC patients, with absence of detectable human anti-human antibody responses	SPECT	[36]
	111In-DTPA-BIWA-IRDye800CW	mAb	Dual-modality imaging improves detection of primary, secondary and metastatic HNSCC	SPECT/CT&FI	[37]
	111In/125I-AbD15179	Fab fragment	111In/125I-AbD15179 both effectively targets CD44v6-expressing HNSCC xenograft	SPECT	[39]
	124I-AbD19384	Fab fragment	124I-AbD19384 has high affinity and target specificity with potential for imaging of CD44v6 antigen expression in vivo	PET/CT	[40]
SSTRs	111In-octreotide	peptide	Case report of 111In-octreotide detected NPC which was misdiagnosed as skull base meningioma	SPECT/CT	[48]
	111In-pentetreotide	peptide	Case report of 111In-pentetreotide for the diagnosis of HNSCC with cervical metastasis	SPECT/CT	[49]
	68Ga-DOTATATE	peptide	SSTR2 expression is a diagnostic and prognostic marker for NPC, which is upregulated by EBV infection	PET/CT	[51]
	68Ga-DOTATATE	peptide	Intense SSTR2 expression is observed in most non-keratinizing NPC, which correlates with 68Ga-DOTATATE uptake	PET/CT	[52]
	68Ga-DOTATATE	peptide	SSTR ligands might be superior to 18F-FDG for EBV-associated NPC PET imaging, particularly at the skull base	PET/CT	[53]
	68Ga-DOTATOC	peptide	68Ga-DOTATOC PET/CT intensity cannot be predicted by IHC, and targeting SSTR in HNSCC does not guarantee a response to PRRT treatment	PET/CT	[54]
	68 Ga-DOTATOC	peptide	Demonstrates tracer uptake in EBV-positive NPC comparable to that in neuroendocrine tumors	PET/CT	[55]
	68Ga-DOTANOC	peptide	Case report in assessing intracranial involvement and differentiating reactive lymph nodes for NPC	PET/CT	[58]
	68Ga-DOTANOC	peptide	Has potential as a newly diagnostic approach for undifferentiated NPC	PET/CT	[59]

¹¹¹In  Indium-111, ¹²⁴I Iodine-124, ¹²⁵I Iodine-125, ¹⁷⁷Lu  Lutetium-177, ⁶⁴Cu Copper-64, ¹⁸⁶Re Rhenium-186, ⁶⁸Ga  Gallium-68, ⁸⁹Zr Zirconium-89, ^99mTc Technetium-99 m, CD44v6 CD44 Exon Variant 6, CT  computed tomography, EBV  Epstein-Barr virus, EGF  epidermal growth factor, EGFR epidermal growth factor receptor, Fab fragment of antigen binding, FI Fluorescence imaging, HNSCC head and neck squamous cell carcinoma, IHC immunohistochemistry, mAb monoclonal antibody, MRI magnetic resonance imaging, NPC nasopharyngeal carcinoma, PET positron emission tomography, PRRT peptide receptor radionuclide therapy, RIT radioimmunotherapy, SPECT single photon emission computed tomography, SSTR somatostatin receptor