Radiolabeled anti-EGFR-antibody improves local tumor control after external beam radiotherapy and offers theragnostic potential

Koi, Lydia; Bergmann, Ralf; Brüchner, Kerstin; Pietzsch, Jens; Pietzsch, Hans‐Jürgen; Krause, Mechthild; Steinbach, Jörg; Zips, Daniel; Baumann, Michaël

doi:10.1016/j.radonc.2013.12.001

Cited by 49 publications

(84 citation statements)

References 32 publications

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“…[32][33][34] Studies from this laboratory and others have reported on the potential of HER1 as a target for molecular imaging and for targeted radiation therapy. [21][22][23][24]26,[35][36][37][38] Cetuximab has been the focus of several imaging studies with the objective of assessing the value of this mAb for disease monitoring, HER1 expression and distribution, patient selection and for performing dosimetric calculations. [23][24][25][26] The preclinical studies from this laboratory demonstrated excellent targeting of s.c. tumor by 111 In-cetuximab given intravenously.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of cetuximab as a candidate for targeted α-particle radiation therapy of HER1-positive disseminated intraperitoneal disease

Milenic

Baidoo

Kim

et al. 2015

mAbs

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Section: Discussionmentioning

confidence: 99%

Evaluation of cetuximab as a candidate for targeted α-particle radiation therapy of HER1-positive disseminated intraperitoneal disease

Milenic

Baidoo

Kim

et al. 2015

mAbs

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“…In addition, for each time point, a 50-mA low-dose CT scan was acquired for attenuation-correction purposes. Corresponding CT images were reconstructed with an image matrix size of 512 · 512 and a voxel size of 1.17 · 1.17 · 5 mm 3 . For the present analysis, all 5 CT scans for each patient were rebinned into a 4 · 4 · 4 mm 3 voxel size to map CT VOIs onto the PET images.…”

Section: Imaging Protocolmentioning

confidence: 99%

“…Another study from the same group demonstrated nearly identical biodistributions of 89 Zribritumomab and 90 Y-ibritumomab (2). Recently, the effect of radioimmunotherapy using 90 Y-cetuximab (combined with external-beam irradiation) on local tumor control in vivo was examined in 3 human squamous cell carcinoma models (3). The latter study showed that PET imaging using 86 Y-cetuximab may be used to assess epidermal growth factor receptor expression, which in turn could be a potential predictor for response to combined radioimmunotherapy and externalbeam radiotherapy.…”

mentioning

confidence: 99%

PET/CT-Derived Whole-Body and Bone Marrow Dosimetry of ⁸⁹Zr-Cetuximab

Makris¹,

Boellaard²,

Lingen³

et al. 2015

J Nucl Med

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PET/CT imaging allows for image-based estimates of organ and red marrow (RM) residence times. The aim of this study was to derive PET/CT-based radiation dosimetry for 89 Zr-cetuximab, with special emphasis on determining RM-absorbed dose. Methods: Seven patients with colorectal cancer received 36.9 ± 0.8 MBq of 89 Zrcetuximab within 2 h after administration of a therapeutic dose of 500 mgÁm −2 of cetuximab. Whole-body PET/CT scans and blood samples were obtained at 1, 24, 48, 94, and 144 h after injection. RM activity concentrations were calculated from manual delineation of the lumbar vertebrae and blood samples, assuming a fixed RMto-plasma activity concentration ratio (RMPR) of 0.19. The cumulated activity was calculated as the area under the curve of the organ time-activity data (liver, lungs, kidneys, spleen, and RM), assuming physical decay after the last scan. The residence time for each organ was derived by dividing the cumulated activity with the total injected activity. The residence time in the remainder of the body was calculated as the maximum possible residence time minus the sum of residence time of source organs, assuming no excretion during the time course of the scans. The (self and total) RM-and organ-absorbed doses and effective whole-body radiation dose were obtained using dose conversion factors from OLINDA/ EXM 1.1. Several simplified 3-time-point dosimetry approaches were also evaluated. Results: The first approach yielded self and total RM doses of 0.17 ± 0.04 and 0.51 ± 0.06 mGyÁMBq −1 , respectively. The second approach deviated by −21% in self-dose and −6% in total dose. RMPR increased over time in 5 of 7 patients. The highest 89 Zr-absorbed dose was observed in the liver with 2.60 ± 0.78 mGyÁMBq −1 , followed by the kidneys, spleen, and lungs, whereas the effective whole-body dose was 0.61 ± 0.09 mSvÁMBq −1 . The simplified 3-time-point (1, 48, and 144 h) dosimetry approach deviated by at most 4% in both organ-absorbed doses and effective dose. Conclusion: Although the total RM dose estimates obtained with the 2 approaches differed only by at most 6%, the image-based approach is preferred because it accounts for nonconstant RMPR. The number of successive scans can be reduced to 3 without affecting effective dose estimates. PETusi ng long-lived radionuclides has proven to be a valuable tool for predicting the biodistribution of labeled monoclonal antibodies (mAbs) (1,2) and organ dosimetry for radioimmunotherapy (2). In addition, the dose-limiting tissue can be determined, enabling dose escalation and optimization of therapeutic treatment planning. In particular, a recent study showed that the biodistributions of 89 ZrDf-cetuximab and 88 Y-DOTA-cetuximab ( 88 Y as a substitute for 90 Y) were comparable for all organs (1). Another study from the same group demonstrated nearly identical biodistributions of 89 Zribritumomab and 90 Y-ibritumomab (2). Recently, the effect of radioimmunotherapy using 90 Y-cetuximab (combined with external-beam irradiation) on local tumor control in vivo was...

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“…Herein, the same therapeutic antibody [cetuximab (Erbitux®, Merck KGaA, Darmstadt, Germany) labelled with 90 Y], and the same panel of head and neck squamous cell carcinoma (HNSCC) cell lines were used. This offers the possibility 65 showed 2 years later that UT-SCC-5 also did not respond to CIERT when compared with EBRT alone in a tumour control analysis in xenografts. This discrepancy between 2D cell cultures and in vivo results is likely caused by the pharmacokinetics of the therapeutic antibody in vivo.…”

Section: Pre-clinical Results: Promises and Challenges Of Combinationmentioning

confidence: 99%

Improving external beam radiotherapy by combination with internal irradiation

Dietrich¹,

Koi²,

Zöphel³

et al. 2015

BJR

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The efficacy of external beam radiotherapy (EBRT) is dose dependent, but the dose that can be applied to solid tumour lesions is limited by the sensitivity of the surrounding tissue. The combination of EBRT with systemically applied radioimmunotherapy (RIT) is a promising approach to increase efficacy of radiotherapy. Toxicities of both treatment modalities of this combination of internal and external radiotherapy (CIERT) are not additive, as different organs at risk are in target. However, advantages of both single treatments are combined, for example, precise high dose delivery to the bulk tumour via standard EBRT, which can be increased by addition of RIT, and potential targeting of micrometastases by RIT. Eventually, theragnostic radionuclide pairs can be used to predict uptake of the radiotherapeutic drug prior to and during therapy and find individual patients who may benefit from this treatment. This review aims to highlight the outcome of pre-clinical studies on CIERT and resultant questions for translation into the clinic. Few clinical data are available until now and reasons as well as challenges for clinical implementation are discussed.

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Radiolabeled anti-EGFR-antibody improves local tumor control after external beam radiotherapy and offers theragnostic potential

Cited by 49 publications

References 32 publications

Evaluation of cetuximab as a candidate for targeted α-particle radiation therapy of HER1-positive disseminated intraperitoneal disease

Evaluation of cetuximab as a candidate for targeted α-particle radiation therapy of HER1-positive disseminated intraperitoneal disease

PET/CT-Derived Whole-Body and Bone Marrow Dosimetry of ⁸⁹Zr-Cetuximab

Improving external beam radiotherapy by combination with internal irradiation

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Radiolabeled anti-EGFR-antibody improves local tumor control after external beam radiotherapy and offers theragnostic potential

Cited by 49 publications

References 32 publications

Evaluation of cetuximab as a candidate for targeted α-particle radiation therapy of HER1-positive disseminated intraperitoneal disease

Evaluation of cetuximab as a candidate for targeted α-particle radiation therapy of HER1-positive disseminated intraperitoneal disease

PET/CT-Derived Whole-Body and Bone Marrow Dosimetry of 89Zr-Cetuximab

Improving external beam radiotherapy by combination with internal irradiation

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PET/CT-Derived Whole-Body and Bone Marrow Dosimetry of ⁸⁹Zr-Cetuximab