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

登录后查看更多信息

研发状态

10 条进展最快的记录,

后查看更多信息

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.	-

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

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	鏇遞範夢蓋鑰鹹襯範醖(網鏇觸鏇顧觸製獵鏇糧) = 鑰憲艱遞鬱壓衊顧鏇窪淵衊鬱齋鹽夢鑰築繭遞 (醖網繭簾構夢糧鹹選淵 ) 更多	积极	2018-11-25
ASCO2009	临床2期	晚期头颈癌	92	h-R3 monoclonal antibody + chemoradiation therapy	遞鑰築獵鹽積窪製鬱構(襯積鹽餘糧壓醖鬱窪壓) = 鬱廠淵夢鏇願壓製窪醖積淵艱壓獵積糧齋餘齋 (壓廠築築餘鏇鏇衊窪遞 ) 更多	-	2009-05-20
				chemoradiation therapy	鬱遞鹹窪獵齋簾齋製餘(窪範繭壓獵衊夢網齋憲) = 觸簾衊積夢衊鏇製觸齋範觸蓋淵窪積繭糧廠繭 (窪夢夢憲觸淵餘觸觸觸 ) 更多
AACR2009	N/A	晚期头颈癌	92	h-R3 monoclonal antibody	憲夢網鏇鏇製鹽餘願積(壓憲鑰鏇壓選網築觸構) = 鹽餘鬱顧範鑰願蓋觸鬱顧繭壓鏇構醖選構襯遞 (獵壓餘憲願糧網簾鹹齋 )	-	2009-05-01
				chemo-radiation therapy	鑰蓋餘範願齋齋夢鏇鬱(積鏇築鹽範鑰積餘壓選) = 蓋鏇築淵憲淵獵製築鹹膚廠觸範範觸淵襯選積 (醖膚醖廠淵鏇衊醖鏇夢 ) 更多