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²¹¹At-Methylene Blue for Targeted Radiotherapy of Human Melanoma Xenografts: Treatment of Cutaneous Tumors and Lymph Node Metastases¹

Department of Chemical Pathology, Division of Molecular Pathology, University College and Middlesex School of Medicine, Cleveland Street, London W1P 6DB [E. M. L.], and Department of Chemistry, University of Birmingham, Edgbaston, Birmingham B15 2TT [R. N. C.], England

The next stage of our preclinical investigations of targeted radiotherapy for melanoma with 3,7-(dimethylamino)phenazathionium chloride [methylene blue (MTB)] labeled with ²¹¹At ( particle emitter) concerns the treatment of cutaneous tumors and their metastases. Fragments of two human melanoma xenografts, highly pigmented HX118 and poorly pigmented HX34, implanted s.c. into nude mice, were treated with four doses of ²¹¹At-MTB injected i.v. The growth rate of cutaneous tumors and the appearance and size of their lymph node metastases served as criteria of treatment effectiveness.

²¹¹At-MTB inhibited the growth of cutaneous tumors in a manner dependent on their pigmentation and initial size. Highly pigmented smaller melanomas were affected by ²¹¹At-MTB to a greater extent than poorly pigmented and larger ones. Growth of the smallest HX118 lesions investigated was completely inhibited for 65 days, whereas the growth inhibition of HX34 tumors of the same size lasted 7 days only. ²¹¹At-MTB exhibited similar pigmentation-dependent effects toward lymph node metastases. The size of metastatic lesions derived from HX118 xenografts never reached that in control animals during the period of observation, whereas those grown from HX34 xenografts attained control values after a 50-day delay.

The results demonstrated the capacity of ²¹¹At-MTB to control the growth of cutaneous melanomas and their metastases.

¹ Supported by the Cancer Research Campaign.

² To whom requests for reprints should be addressed.

Received 10/28/91. Accepted 6/ 9/92.