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

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

doi:10.2967/jnumed.114.148296

Cited by 19 publications

(13 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We found that the tumor TLG, taking into account volume-based and glucose metabolism, demonstrates the ability of early prediction for the tumor response to radiation treatment, which was not observed in the SUVmax of tumors. Our results were supported by Dijk et al [ 35 , 36 ], showing that the SUVmax [ 18 F]FDG uptake not significantly changed in murine squamous cell carcinoma at Day 7 after a dose of 10 or 20 Gy irradiation. Compared to SUVmax, TLG was found to be a better prognostic indicator of oncological outcomes when [ 18 F]FDG PET/CT performed during radiation therapy in soft-tissue sarcoma and locally advanced head and neck squamous cell carcinoma [ 29 , 30 ].…”

Section: Discussionsupporting

confidence: 90%

Early Response Monitoring Following Radiation Therapy by Using [18F]FDG and [11C]Acetate PET in Prostate Cancer Xenograft Model with Metabolomics Corroboration

et al. 2017

View full text Add to dashboard Cite

We aim to characterize the metabolic changes associated with early response to radiation therapy in a prostate cancer mouse model by 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) and [11C]acetate ([11C]ACT) positron emission tomography, with nuclear magnetic resonance (NMR) metabolomics corroboration. [18F]FDG and [11C]ACT PET were performed before and following irradiation (RT, 15Gy) for transgenic adenocarcinoma of mouse prostate xenografts. The underlying metabolomics alterations of tumor tissues were analyzed by using ex vivo NMR. The [18F]FDG total lesion glucose (TLG) of the tumor significant increased in the RT group at Days 1 and 3 post-irradiation, compared with the non-RT group (p < 0.05). The [11C]ACT maximum standard uptake value (SUVmax) in RT (0.83 ± 0.02) and non-RT groups (0.85 ± 0.07) were not significantly different (p > 0.05). The ex vivo NMR analysis showed a 1.70-fold increase in glucose and a 1.2-fold increase in acetate in the RT group at Day 3 post-irradiation (p < 0.05). Concordantly, the expressions of cytoplasmic acetyl-CoA synthetase in the irradiated tumors was overexpressed at Day 3 post-irradiation (p < 0.05). Therefore, TLG of [18F]FDG in vivo PET images can map early treatment response following irradiation and be a promising prognostic indicator in a longitudinal preclinical study. The underlying metabolic alterations was not reflected by the [11C]ACT PET.

show abstract

Section: Discussionsupporting

confidence: 90%

Early Response Monitoring Following Radiation Therapy by Using [18F]FDG and [11C]Acetate PET in Prostate Cancer Xenograft Model with Metabolomics Corroboration

et al. 2017

View full text Add to dashboard Cite

show abstract

“…In head and neck squamous cell carcinomas (HNSCC), overexpression of EGFR is associated with relapse after radiotherapy 6 and can be used for selection of patients for hyperfractionated accelerated radiotherapy 7 . Preclinical studies suggest that determination of EGFR expression can be used for monitoring of response to combination of radiation therapy and cetuximab in HNSCC 8 or to therapy using heat shock protein 90 inhibitors 9 . Radionuclide molecular imaging is a potential method for in vivo measurement of EGFR expression in malignant tumours.…”

Section: Introductionmentioning

confidence: 99%

The use of radiocobalt as a label improves imaging of EGFR using DOTA-conjugated Affibody molecule

Garousi

Andersson

Dam

et al. 2017

Sci Rep

View full text Add to dashboard Cite

Several anti-cancer therapies target the epidermal growth factor receptor (EGFR). Radionuclide imaging of EGFR expression in tumours may aid in selection of optimal cancer therapy. The 111In-labelled DOTA-conjugated ZEGFR:2377 Affibody molecule was successfully used for imaging of EGFR-expressing xenografts in mice. An optimal combination of radionuclide, chelator and targeting protein may further improve the contrast of radionuclide imaging. The aim of this study was to evaluate the targeting properties of radiocobalt-labelled DOTA-ZEGFR:2377. DOTA-ZEGFR:2377 was labelled with 57Co (T1/2 = 271.8 d), 55Co (T1/2 = 17.5 h), and, for comparison, with the positron-emitting radionuclide 68Ga (T1/2 = 67.6 min) with preserved specificity of binding to EGFR-expressing A431 cells. The long-lived cobalt radioisotope 57Co was used in animal studies. Both 57Co-DOTA-ZEGFR:2377 and 68Ga-DOTA-ZEGFR:2377 demonstrated EGFR-specific accumulation in A431 xenografts and EGFR-expressing tissues in mice. Tumour-to-organ ratios for the radiocobalt-labelled DOTA-ZEGFR:2377 were significantly higher than for the gallium-labelled counterpart already at 3 h after injection. Importantly, 57Co-DOTA-ZEGFR:2377 demonstrated a tumour-to-liver ratio of 3, which is 7-fold higher than the tumour-to-liver ratio for 68Ga-DOTA-ZEGFR:2377. The results of this study suggest that the positron-emitting cobalt isotope 55Co would be an optimal label for DOTA-ZEGFR:2377 and further development should concentrate on this radionuclide as a label.

show abstract

“…However, HER2 expression in HNSCC is negligible and cannot be used as a biomarker for treatment outcomes in this patient group. Instead, overexpression of EGFR is common in HNSCC patients [ 4 , 11 ], indicating that targeting EGFR could be a suitable approach. Wild-type EGFR has been shown to be a client protein of HSP90 [ 12 ] suggesting that their interaction is vital for the proliferation of EGFR-dependent cancers.…”

Section: Introductionmentioning

confidence: 99%

Molecular imaging of EGFR and CD44v6 for prediction and response monitoring of HSP90 inhibition in an in vivo squamous cell carcinoma model

Spiegelberg

Mortensen

Selvaraju

et al. 2015

Eur J Nucl Med Mol Imaging

View full text Add to dashboard Cite

PurposeHeat shock protein 90 (HSP90) is essential for the activation and stabilization of numerous oncogenic client proteins. AT13387 is a novel HSP90 inhibitor promoting degradation of oncogenic proteins upon binding, and may also act as a radiosensitizer. For optimal treatment there is, however, the need for identification of biomarkers for patient stratification and therapeutic response monitoring, and to find suitable targets for combination treatments. The aim of this study was to assess the response of surface antigens commonly expressed in squamous cell carcinoma to AT13387 treatment, and to find suitable biomarkers for molecular imaging and radioimmunotherapy in combination with HSP90 inhibition.MethodsCancer cell proliferation and radioimmunoassays were used to evaluate the effect of AT13387 on target antigen expression in vitro. Inhibitor effects were then assessed in vivo in mice-xenografts. Animals were treated with AT13387 (5 × 50 mg/kg), and were imaged with PET using either 18F-FDG or 124I-labelled tracers for EGFR and CD44v6, and this was followed by ex-vivo biodistribution analysis and immunohistochemical staining.ResultsAT13387 exposure resulted in high cytotoxicity and possible radiosensitization with IC50 values below 4 nM. Both in vitro and in vivo AT13387 effectively downregulated HSP90 client proteins. PET imaging with 124I-cetuximab showed a significant decrease of EGFR in AT13387-treated animals compared with untreated animals. In contrast, the squamous cell carcinoma-associated biomarker CD44v6, visualized with 124I-AbD19384 as well as 18F-FDG uptake, were not significantly altered by AT13387 treatment.ConclusionWe conclude that AT13387 downregulates HSP90 client proteins, and that molecular imaging of these proteins may be a suitable approach for assessing treatment response. Furthermore, radioimmunotherapy targeting CD44v6 in combination with AT13387 may potentiate the radioimmunotherapy outcome due to radiosensitizing effects of the drug, and could potentially lead to a lower dose to normal tissues.Electronic supplementary materialThe online version of this article (doi:10.1007/s00259-015-3260-x) contains supplementary material, which is available to authorized users.

show abstract

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

Cited by 19 publications

References 31 publications

Early Response Monitoring Following Radiation Therapy by Using [18F]FDG and [11C]Acetate PET in Prostate Cancer Xenograft Model with Metabolomics Corroboration

Early Response Monitoring Following Radiation Therapy by Using [18F]FDG and [11C]Acetate PET in Prostate Cancer Xenograft Model with Metabolomics Corroboration

The use of radiocobalt as a label improves imaging of EGFR using DOTA-conjugated Affibody molecule

Molecular imaging of EGFR and CD44v6 for prediction and response monitoring of HSP90 inhibition in an in vivo squamous cell carcinoma model

Contact Info

Product

Resources

About