Assessing Tumor Hypoxia in Head and Neck Cancer by PET With 62Cu-Diacetyl-Bis(N4-Methylthiosemicarbazone)

Sato, Yoshitaka; Tsujikawa, Tetsuya; Oh, Myungmi; Mori, Tetsuya; Kiyono, Yasushi; Fujieda, Shigeharu; Kimura, Hirohiko; Okazawa, Hidehiko

doi:10.1097/rlu.0000000000000537

Cited by 23 publications

(20 citation statements)

References 33 publications

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“…19). This was supported by results from another recent study in which high pretreatment 62 Cu-ATSM tumor uptake correlated with a reduced PFS (20). However, it is not known to what extent Cu-ATSM reflects tumor hypoxia is questionable.…”

Section: Hypoxiasupporting

confidence: 55%

PET Imaging in Head and Neck Cancer Patients to Monitor Treatment Response: A Future Role for EGFR-Targeted Imaging

Dijk

Boerman

Kaanders

et al. 2015

Clinical Cancer Research

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Approximately 50,000 new cases of head and neck squamous cell carcinoma (HNSCC) are diagnosed worldwide each year and subsequently treated with surgery, chemotherapy, radiotherapy, and/or targeted therapy. The heterogeneity of the patient population in terms of treatment response drives the search for tumorspecific biomarkers. Imaging of biomarkers can reveal patientspecific responses to therapies and, if assessed early after the start of treatment, may allow adaptation of treatment regimens. In this review, tracers that have been tested to monitor treatment efficacy in HNSCC by PET scanning prior to and early after the onset of treatment are discussed. An important imaging target for this application in HNSCC patients is the EGFR. It steers the pathways related to proliferation, hypoxia, DNA damage repair, and apoptosis, all treatment-resistance mechanisms. The anti-EGFR antibody cetuximab has been labeled with various radionuclides and has been tested as an imaging biomarker in several HNSCC models. These studies suggest that EGFR-targeting tracers can be used to monitor EGFR receptor expression in HNSCC and have the potential to noninvasively monitor cetuximab treatment and steer individualized treatment regimens. Multiple factors can influence the uptake of EGFR-targeting tracers. Here, we discuss the relevance of gene and protein overexpression, mutations, and amplifications related to EGFR signaling. In addition, monoclonal antibody properties and the effect on the host immune system are reviewed in light of the future role of EGFR-targeted imaging in HNSCC.

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Section: Hypoxiasupporting

confidence: 55%

PET Imaging in Head and Neck Cancer Patients to Monitor Treatment Response: A Future Role for EGFR-Targeted Imaging

Dijk

Boerman

Kaanders

et al. 2015

Clinical Cancer Research

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“…Minagawa et al (2011) found that 62 Cu-ATSM SUV max , but not TMR, was significantly different in 17 locally advanced head and neck cancer patients with and without residual or recurrent tumours. A study of 25 head and neck cancer patients indicated that both increasing SUV max and TMR were associated with worse progression-free survival (Sato et al , 2014). Grassi et al (2014) used 64 Cu-ATSM to define a biological target volume in 11 patients with HNSCC and found this parameter, along with SUV max , to have high sensitivity but low specificity in predicting complete response to therapy.…”

Section: Discussionmentioning

confidence: 99%

“…Although the exact mechanism has not been elucidated and uptake may be dependent on cell or tumour type, clinical studies have clearly demonstrated the potential as an imaging biomarker that warrants further investigation, especially in HNSCC, with clear advantages over the nitroimidazole-based hypoxia tracers (Minagawa et al , 2011; Grassi et al , 2014; Sato et al , 2014). …”

mentioning

confidence: 99%

Association between hypoxic volume and underlying hypoxia-induced gene expression in oropharyngeal squamous cell carcinoma

et al. 2017

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Background:Hypoxia imaging is a promising tool for targeted therapy but the links between imaging features and underlying molecular characteristics of the tumour have not been investigated. The aim of this study was to compare hypoxia biomarkers and gene expression in oropharyngeal squamous cell carcinoma (OPSCC) diagnostic biopsies with hypoxia imaged with 64Cu-ATSM PET/CT.Methods:64Cu-ATSM imaging, molecular and clinical data were obtained for 15 patients. Primary tumour SUVmax, tumour to muscle ratio (TMR) and hypoxic volume were tested for association with reported hypoxia gene signatures in diagnostic biopsies. A putative gene signature for hypoxia in OPSCCs (hypoxic volume-associated gene signature (HVS)) was derived.Results:Hypoxic volume was significantly associated with a reported hypoxia gene signature (rho=0.57, P=0.045), but SUVmax and TMR were not. Immunohistochemical staining with the hypoxia marker carbonic anhydrase 9 (CA9) was associated with a gene expression hypoxia response (rho=0.63, P=0.01). Sixteen genes were positively and five genes negatively associated with hypoxic volume (adjusted P<0.1; eight genes had adjusted P<0.05; HVS). This signature was associated with inferior 3-year progression-free survival (HR=1.5 (1.0–2.2), P=0.047) in an independent patient cohort.Conclusions:64Cu-ATSM-defined hypoxic volume was associated with underlying hypoxia gene expression response. A 21-gene signature derived from hypoxic volume from patients with OPSCCs in our study may be linked to progression-free survival.

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“…Furthermore, clinical trials are also underway to assess the value of 18 F-HX4-PET in identifying microenvironment-associated treatment response in pancreatic (NCT01989000), head and neck (NCT01347281), and cervical cancers (NCT02233387). Lastly, uptake of the non-nimorazole PET marker Cu-ATSM has also been clinically correlated with therapeutic response in numerous tumor types, including lung [133,134], brain [135], and cervical cancers [134]. However, Cu-ATSM is not a direct marker of hypoxia and its mechanism is still largely unknown.…”

Section: Assessment Of Hypoxia and Treatment Responsementioning

confidence: 99%

Integration of imaging into clinical practice to assess the delivery and performance of macromolecular and nanotechnology-based oncology therapies

Spence

Souza

Dou

et al. 2015

Journal of Controlled Release

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Assessing Tumor Hypoxia in Head and Neck Cancer by PET With 62Cu-Diacetyl-Bis(N4-Methylthiosemicarbazone)

Abstract: Pretreatment ⁶²Cu-ATSM PET is useful for predicting the prognosis of patients with HNC.

Cited by 23 publications

References 33 publications

PET Imaging in Head and Neck Cancer Patients to Monitor Treatment Response: A Future Role for EGFR-Targeted Imaging

PET Imaging in Head and Neck Cancer Patients to Monitor Treatment Response: A Future Role for EGFR-Targeted Imaging

Association between hypoxic volume and underlying hypoxia-induced gene expression in oropharyngeal squamous cell carcinoma

Integration of imaging into clinical practice to assess the delivery and performance of macromolecular and nanotechnology-based oncology therapies

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