作者: Schreiner, Lena ; Löck, Steffen ; Andreeff, Michael ; Freudenberg, Robert ; Pietzsch, Hans-Jürgen ; Koi, Lydia ; Sihver, Wiebke ; Bergmann, Ralf ; Dietrich, Antje ; Kotzerke, Jörg ; Schubert, Maik ; Hering, Sandra ; Steinbach, Jörg ; Baumann, Michael ; Krause, Mechthild

BACKGROUND AND PURPOSE:

Systemic molecular radiotherapy utilizes internal irradiation by radionuclide-labeled tumor-targeting agents with the potential to destroy (micro-)metastases. However, doses that are applicable in solid tumors do not reach the levels nessecary for tumor control. Thus, the combination of molecular and external radiotherapy is a promising treatment strategy, as enhanced tumor doses can be delivered with and without minor overlapping toxicities. Here, we combined a ⁹⁰Y-labeled anti-EGFR antibody (Cetuximab) with clinically relevant fractionated radiotherapy in a preclinical trial using head and neck squamous cell carcinoma xenograft tumors.

MATERIALS AND METHODS:

To model ⁹⁰Y-Cetuximab uptake for treatment schedule optimization, FaDu-bearing mice were injected with near-infrared-labeled-Cetuximab at different time points during radiotherapy with differing doses. Cetuximab uptake was longitudinally followed by in vivo-optical imaging. Tumor control probability experiments with fractionated radiotherapy (30 fx, 6 weeks, 8 dose groups/ arm) in combination with ⁹⁰Y-Cetuximab were performed to test the curative potential.

RESULTS:

Imaging of near-infrared-labeled-Cetuximab uptake revealed that low to moderate external beam doses can enhance antibody uptake. Using the optimized schedule, combination of molecular and external radiotherapy using ⁹⁰Y-Cetuximab at a dose that did not result in permanent tumor inactivation in previous experiments, led to substantially increased tumor control compared to radiotherapy alone.

CONCLUSION:

Our results indicate that combination of radiolabeled therapeutics with clinically relevant fractionated radiotherapy has a remarkable potential to improve curative treatment outcome. Application of some radiation dose prior to injection may improve drug uptake and enable patient stratification and treatment personalization via a corresponding PET-tracer during therapy.

1978-04-01·Annals of the rheumatic diseases1区 · 医学

Intra-articular yttrium 90 in rabbits. Comparison of behaviour of various radiocolloids in rabbits and in man.

1区 · 医学

Article

作者: Gumpel, J. M.

Comparative studies of the retention of various yttrium 90 radiocolloids and of noncolloidal yttrium 90 chloride were performed in rabbits with arthritis induced in one knee. Two colloids, the citrate and resin forms, showed a statistically significant difference in retention between inflamed and normal knees, isotope being retained better in the normal knee. Marked differences were found in the handling of the various yttrium preparations in rabbits compared with previously reported results in man. These differences suggest that the rabbit with induced arthritis is not a suitable model in which to test retention of different radiocolloids before use in man.

100 项与 Anti-EGFR monoclonal antibody-Y-90 相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
胶质瘤	临床1期	古巴	CIMYM Biosciences, Inc.	-
胶质瘤	临床1期	意大利	-	-
胶质瘤	临床1期	-	Gilead Sciences, Inc.	-

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


Austin 04888 (ESMO_ASIA2018)	N/A	葡萄膜黑色素瘤巩固	10	Intrahepatic Yttrium-90 microsphere radioembolisation + Intravenous cisplatin	鑰淵範選鑰鹹餘壓範蓋(淵構壓齋糧鹹願網築衊) = 積膚淵廠鏇餘廠餘膚顧膚膚襯齋觸醖鑰築淵觸 (廠艱繭艱淵鹽積繭艱蓋 ) 更多	积极	2018-11-25
ASCO2009	临床2期	晚期头颈癌	92	h-R3 monoclonal antibody + chemoradiation therapy	淵鬱選積鹹壓壓遞艱淵(廠壓遞鏇艱簾選鑰鹽獵) = 鹽膚餘顧淵艱齋積觸構範壓鹽齋齋簾淵夢憲選 (獵築憲構鏇選鑰網鹹遞 ) 更多	-	2009-05-20
				chemoradiation therapy	選鑰選網鏇繭鏇齋膚衊(壓淵製蓋膚網鏇選選憲) = 構夢齋範齋鏇鹽築憲網襯製衊觸範顧鏇糧鹽餘 (衊網獵繭獵獵膚餘艱淵 ) 更多
AACR2009	N/A	晚期头颈癌	92	h-R3 monoclonal antibody	繭壓憲築鹽構顧範襯範(遞憲選糧廠鹽製製鬱襯) = 淵膚衊製鑰餘願艱獵築蓋獵襯窪餘窪觸鑰糧衊 (膚餘鏇觸醖遞遞構簾選 )	-	2009-05-01
				chemo-radiation therapy	蓋齋憲憲積觸鬱衊選艱(廠簾遞鹽選膚窪製膚膚) = 顧構簾鹽憲壓繭窪齋獵餘壓網夢鹹醖襯鹹網網 (窪積繭夢願壓鑰衊淵構 ) 更多