Early Response Monitoring with <sup>18</sup>F-FDG PET and Cetuximab-F(ab′)<sub>2</sub>-SPECT After Radiotherapy of Human Head and Neck Squamous Cell Carcinomas in a Mouse Model

Dijk, Laura K. van; Boerman, Otto C.; Franssen, Gerben M.; Lok, Jasper; Kaanders, Johannes H.A.M.; Bussink, Johan

doi:10.2967/jnumed.114.141762

Cited by 12 publications

(26 citation statements)

References 39 publications

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“…A significant increase in 111 In-cetuximab-F(ab9) 2 uptake in the tumor 2.5 wk after treatment was seen in tumors resistant to therapy. For radiationresistant SCCNij202, we found an increase of tracer uptake in irradiated tumors along with an increase in iEGFR, which points to an increase in membrane receptor availability, as described previously (23). This increase of tumor uptake may represent a compensation mechanism for which the increase in systemically available EGFR enhances EGFR signaling promoting cell survival, especially in a heavily EGFR-reliant tumor model such as SCCNij202.…”

Section: Discussionsupporting

confidence: 48%

“…In a previous study, we assessed the response to irradiation with 111 In-cetuximab-F(ab9) 2 imaging in SCCNij202 and SCCNij167 (23). As these 2 models portray clinical extremes in cetuximab response and high EGFR (SCCNij202) versus low EGFR (SCCNij167), it was deemed of added value to investigate a model with moderate EGFR expression and cetuximab nonresponse.…”

Section: Discussionmentioning

confidence: 99%

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¹¹¹In-Cetuximab-F(ab′)₂ SPECT and ¹⁸F-FDG PET for Prediction and Response Monitoring of Combined-Modality Treatment of Human Head and Neck Carcinomas in a Mouse Model

et al. 2014

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Section: Discussionsupporting

confidence: 48%

Section: Discussionmentioning

confidence: 99%

¹¹¹In-Cetuximab-F(ab′)₂ SPECT and ¹⁸F-FDG PET for Prediction and Response Monitoring of Combined-Modality Treatment of Human Head and Neck Carcinomas in a Mouse Model

et al. 2014

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“…Tumor uptake of 64 Cu-cetuximab-F(ab′) 2 in terms of % ID/g was similar to that of the 111 In-labeled cetuximab-F(ab′) 2 tracer as described previously (13)(14)(15). Cetuximab has been radiolabeled with 64 Cu in several other studies, using DOTA as a chelator (22)(23)(24)(25)(26)(27).…”

Section: Discussionmentioning

confidence: 89%

“…Irradiated SCCNij202 tumors exhibited an increase in 111 In-cetuximab-F(ab′) 2 uptake up to 14 days after treatment, which correlated with an increase of available membranous EGFR as determined immunohistochemically (15). Intratumoral localization of EGFR in HNSCCs is heterogeneous, and to allow accurate tracer quantification and reduction of partial volume effects it is necessary to acquire high-resolution images.…”

Section: Discussionmentioning

confidence: 99%

“…Previous in vivo studies have shown that 111 In-cetuximab-F(ab′) 2 can visualize EGFR accessibility in mice. It displayed a differential uptake in head and neck xenografts, with varying levels of EGFR expression and differential response to treatment with radiotherapy and/or cetuximab (13)(14)(15). The aim of this study is to develop a PET-based imaging agent with clinical perspective for imaging EGFR, as PET has a higher resolution and allows more accurate quantitative analyses of images than SPECT (16).…”

Section: Introductionmentioning

confidence: 99%

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PET of EGFR with ⁶⁴Cu‐cetuximab‐F(ab′)₂ in mice with head and neck squamous cell carcinoma xenografts

Dijk

Yim

Franssen

et al. 2015

Contrast Media & Molecular

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a Overexpression of the epidermal growth factor receptor (EGFR) is linked to an adverse outcome in various solid tumors. Cetuximab is an EGFR inhibitor, which in combination with radiotherapy improves locoregional control and survival in a subgroup of patients with head and neck squamous cell carcinomas (HNSCCs). The aim of this study was to develop and characterize an EGFR-directed PET tracer, 64 Cu-cetuximab-F(ab′) 2 , to determine the systemic accessibility of EGFR. Mice with HNSCC xenografts, UT-SCC-8 (n = 6) or UT-SCC-45 (n = 6), were imaged 24 h post injection with 64 Cu-NODAGA-cetuximab-F(ab′) 2 using PET/CT. One mouse for each tumor model was co-injected with excess unlabeled cetuximab 3 days before radiotracer injection to determine non-EGFR-mediated uptake. Ex vivo biodistribution of the tracer was determined and tumors were analyzed by autoradiography and immunohistochemistry. The SUV max of UT-SCC-8 tumors was higher than that of UT-SCC-45: 1.5 ± 1.0 and 0.8 ± 0.2 (p < 0.05), respectively. SUV max after in vivo blocking of EGFR with cetuximab was 0.4. Immunohistochemistry showed that UT-SCC-8 had a significantly higher EGFR expression than UT-SCC-45: 0.50 ± 0.19 versus 0.12 ± 0.08 (p < 0.005), respectively. Autoradiography indicated that 64 Cu-cetuximab-F(ab′) 2 uptake correlated with EGFR expression in both tumors: r = 0.86 ± 0.06 (UT-SCC-8) and 0.90 ± 0.06 (UT-SCC-45).64 Cu-cetuxmab-F(ab′) 2 is a promising PET tracer to determine expression of EGFR in vivo. Clinically, this tracer has the potential to be used to determine cetuximab targeting of tumors and possibly to non-invasively monitor the response to EGFR-inhibitor treatment.

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Evaluation of 18F‐FDG PET/CT as an early imaging biomarker for response monitoring after radiochemotherapy using cetuximab in head and heck squamous cell carcinoma

et al. 2019

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Background: To determine whether 18 F-PET/CT is able to identify treatment response as early as 1 week after the end of chemoradiotherapy, whether 18 F-PET/ CT can identify prognostic markers concerning progression free survival and can identify patients who need additional consolidation therapy. Methods: A total of 54 patients with head and neck cancer were prospectively enrolled in this single-center, randomized study from 03/2012-04/2015. Patients underwent FDG-PET/CT imaging at three predefined time points: pretreatment (PET/CT1), 1 week postprimary radiochemotherapy (PET/CT2) and 3 months postprimary radiochemotherapy (PET/CT3). Tumors were assessed quantitatively based on size and glucose uptake (SUVmax) concerning response at each time point. Response assessment was correlated with progression free survival. All patients had a minimum follow-up period of 18 months. Multivariate regression analysis was performed to find independent predictors for progression free survival (PFS). Results: Thirty-two (32) patients (64%) overall remained disease free, 11 patients (22%) had recurrence and 7 patients (14%) had persistent disease. There was no significantly different metabolic parameter ratio found concerning responders and nonresponders at posttreatment (PET/CT2 and 3) time points (P > .05) during clinical follow-up. Multivariate regression analysis demonstrated both SUVmax and diameter assessed at time point PET/CT3 represent independent predictors of progression free survival (PFS). There was also no statistically significant difference in PFS between responders and nonresponders by means of PET/CT2 in both study arms (P > .05). Imaging responders at time point PET/CT3 showed a significantly longer PFS compared to nonresponders after the end of consolidation therapy (P < .01). Conclusions: Early response of head/neck cancer after radiochemotherapy can be accurately assessed with PET/CT 1 week after RCT. SUVmax and lesion diameter are independent predictors of PFS at time point PET/CT3. PET/CT2 has no

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Early Response Monitoring with ¹⁸F-FDG PET and Cetuximab-F(ab′)₂-SPECT After Radiotherapy of Human Head and Neck Squamous Cell Carcinomas in a Mouse Model

Cited by 12 publications

References 39 publications

¹¹¹In-Cetuximab-F(ab′)₂ SPECT and ¹⁸F-FDG PET for Prediction and Response Monitoring of Combined-Modality Treatment of Human Head and Neck Carcinomas in a Mouse Model

¹¹¹In-Cetuximab-F(ab′)₂ SPECT and ¹⁸F-FDG PET for Prediction and Response Monitoring of Combined-Modality Treatment of Human Head and Neck Carcinomas in a Mouse Model

PET of EGFR with ⁶⁴Cu‐cetuximab‐F(ab′)₂ in mice with head and neck squamous cell carcinoma xenografts

Evaluation of 18F‐FDG PET/CT as an early imaging biomarker for response monitoring after radiochemotherapy using cetuximab in head and heck squamous cell carcinoma

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Early Response Monitoring with 18F-FDG PET and Cetuximab-F(ab′)2-SPECT After Radiotherapy of Human Head and Neck Squamous Cell Carcinomas in a Mouse Model

Cited by 12 publications

References 39 publications

111In-Cetuximab-F(ab′)2 SPECT and 18F-FDG PET for Prediction and Response Monitoring of Combined-Modality Treatment of Human Head and Neck Carcinomas in a Mouse Model

111In-Cetuximab-F(ab′)2 SPECT and 18F-FDG PET for Prediction and Response Monitoring of Combined-Modality Treatment of Human Head and Neck Carcinomas in a Mouse Model

PET of EGFR with 64Cu‐cetuximab‐F(ab′)2 in mice with head and neck squamous cell carcinoma xenografts

Evaluation of 18F‐FDG PET/CT as an early imaging biomarker for response monitoring after radiochemotherapy using cetuximab in head and heck squamous cell carcinoma

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Early Response Monitoring with ¹⁸F-FDG PET and Cetuximab-F(ab′)₂-SPECT After Radiotherapy of Human Head and Neck Squamous Cell Carcinomas in a Mouse Model

¹¹¹In-Cetuximab-F(ab′)₂ SPECT and ¹⁸F-FDG PET for Prediction and Response Monitoring of Combined-Modality Treatment of Human Head and Neck Carcinomas in a Mouse Model

¹¹¹In-Cetuximab-F(ab′)₂ SPECT and ¹⁸F-FDG PET for Prediction and Response Monitoring of Combined-Modality Treatment of Human Head and Neck Carcinomas in a Mouse Model

PET of EGFR with ⁶⁴Cu‐cetuximab‐F(ab′)₂ in mice with head and neck squamous cell carcinoma xenografts