Author: Löck, Steffen ; Schreiner, Lena ; Andreeff, Michael ; Freudenberg, Robert ; Koi, Lydia ; Pietzsch, Hans-Jürgen ; 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.

01 Apr 1978·Annals of the rheumatic diseasesQ1 · MEDICINE

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

Q1 · MEDICINE

Article

Author: 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 Deals associated with Anti-EGFR monoclonal antibody-Y-90

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Indication	Highest Phase	Country/Location	Organization	Date
Glioma	Phase 1	CU	CIMYM Biosciences, Inc.	-
Glioma	Phase 1	IT	-	-
Glioma	Phase 1	-	Gilead Sciences, Inc.	-

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


Austin 04888 (ESMO_ASIA2018)	Not Applicable	Uveal Melanoma Consolidation	10	Intrahepatic Yttrium-90 microsphere radioembolisation + Intravenous cisplatin	otfbjabbkx(vfzryogkvj) = ytjvpviuyy qltcacvzqt (kbhovlyoaw ) View more	Positive	25 Nov 2018
ASCO2009	Phase 2	Advanced Head and Neck Carcinoma	92	h-R3 monoclonal antibody + chemoradiation therapy	hqxyqcibvs(bilcurndck) = tqzkloedvx tbwnppnbzo (bxumyfkxre ) View more	-	20 May 2009
				chemoradiation therapy	jqwwxapuun(oenpjhrctv) = iseogpzlai bmvyuhkecc (rpmvbjcjtd ) View more
AACR2009	Not Applicable	Advanced Head and Neck Carcinoma	92	h-R3 monoclonal antibody	fuzooepupb(inodgopghf) = stzpauveat mfekftyoyk (ajjfjwzmvh )	-	01 May 2009
				chemo-radiation therapy	dgzjgmpvjl(ykbvjyyasy) = emsgfsajow ppfgiwqsxr (exykqqpvps ) View more

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Anti-EGFR monoclonal antibody-Y-90

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