Introduction
Head and neck cancer and its treatment
Targeted therapy for HNSCC
Molecular imaging for targeted therapy
Nuclear medicine-based molecular imaging and its potential for HNSCC patients
Molecular imaging targeting tumor cells 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 | ||
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] |
Imaging of EGFR
Monitor HNSCC treatment using EGFR-targeted molecular imaging
Theranostic targeting of EGFR
Imaging of CD44v6
Antibody-based targeting of CD44v6
Recombinant antibody-based targeting of CD44v6
Imaging of somatostatin receptors
Molecular imaging targeting tumor microenvironment in HNSCC
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] |
Imaging of CAFs
Assessment of primary tumor of HNSCC using 68Ga-FAPI imaging
Assessment of locoregional and distant metastasis of HNSCC using 68Ga-FAPI imaging
Imaging of programmed cell death protein 1 and its ligand
Molecular imaging targeting tumor angiogenesis in HNSCC
Targets | Targeted Imaging Agent | Results | Imaging Technique | Refs. |
---|---|---|---|---|
Integrins | 18F-Galacto-RGD | Image fusion of 18F-Galacto-RGD PET with MRI or multi-slice CT allows for definition of tumor subvolumes with intense tracer uptake | PET | [107] |
68Ga-DOTA-E-[c(RGDfK)]2 | Could detect αvβ3 integrin expression in OSCC patients with adequate TBRs | PET/CT | [108] | |
68Ga-NODAGA-RGD | 68Ga-NODAGA-RGD uptake has a different spatial distribution than 18F-FDG bringing different tumor information, and is not related to tumor grade, p16, or HPV status | PET/CT | [109] | |
111In-RGD2 | Allows in vivo monitoring of angiogenic responses after radiotherapy, and its uptake in HNSCC was not affected by anti-angiogenic drug therapy | PET/CT | [111] | |
68Ga-NODAGA-c(RGDfK) | Uptake of radiolabeled RGD peptides is not necessarily decreased by effective bevacizumab antiangiogenic therapy | PET/CT | [112] | |
18F-RGD-K5 | Demonstrates the feasibility of identifying incomplete response to concurrent CRT in HNSCC patients using RGD PET/CT | PET/CT | [113] | |
PSMA | 111In-J591 | Has potential as a targeting agent for solid tumor vasculature and lesion detection in HNSCC | gamma camera & SPECT | [120] |
68Ga-PSMA | Case report of incidental detection of oropharynx SCC | PET/CT | [121] | |
68Ga-PSMA | Detection of synchronous primary tongue base SCC in patients with prostate cancer | PET/CT | [122] |