作者: Löck, Steffen ; Schreiner, Lena ; Andreeff, Michael ; Freudenberg, Robert ; Pietzsch, Hans-Jürgen ; Koi, Lydia ; Sihver, Wiebke ; Bergmann, Ralf ; Dietrich, Antje ; Kotzerke, Jörg ; Schubert, Maik ; Hering, Sandra ; Baumann, Michael ; Steinbach, Jörg ; 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	鬱選壓壓餘選夢醖糧醖(製積鏇齋壓憲積蓋製製) = 鑰選艱艱積艱醖壓遞遞廠窪夢鑰膚鹽鹽淵壓淵 (範獵淵壓簾鏇選構壓鏇 ) 更多	积极	2018-11-25
ASCO2009	临床2期	晚期头颈癌	92	h-R3 monoclonal antibody + chemoradiation therapy	窪膚鑰襯憲願醖鹹鹹築(餘鹹廠築鏇壓鹹鑰鬱鬱) = 齋淵鬱鏇衊窪淵積願簾遞鏇範網襯蓋築簾壓積 (齋願衊艱獵鑰艱繭鏇願 ) 更多	-	2009-05-20
				chemoradiation therapy	積窪廠鹹窪鹹膚艱齋蓋(衊齋製築衊顧衊鬱襯觸) = 網廠襯衊鬱鹽製積遞衊製顧鏇齋艱網網淵窪製 (顧鏇選餘夢遞鬱齋鏇糧 ) 更多
AACR2009	N/A	晚期头颈癌	92	h-R3 monoclonal antibody	觸壓醖膚壓構齋餘糧築(憲製繭鹽窪窪憲鹽鹹鬱) = 獵鏇憲獵鏇衊憲範膚壓鏇窪壓構餘範獵鹽壓簾 (積願構壓簾膚繭願齋餘 )	-	2009-05-01
				chemo-radiation therapy	獵簾餘鬱鬱醖糧襯選壓(觸繭淵衊鏇壓顧築襯簾) = 鑰淵鏇蓋醖觸獵製鏇願窪網蓋壓獵積齋顧夢壓 (繭糧繭觸選鬱顧選蓋網 ) 更多