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Radioactivity from Labeled Precursors of Melanin in Mice and Hamsters with Melanomas¹

Department of Internal Medicine (Nuclear Medicine), University of Michigan Medical School and the School of Pharmacy, Ann Arbor, Michigan 48104

In a repetition of the work of Blois and Kallman and of Hempel and Deimel studying the tissue distribution of radioactivity concentration following injections in mice with melanomas of DL-3,4-dihydroxyphenylalanine-2-¹⁴C (dopa), DL-dopa-1-¹⁴C, and L-dopa-³H, little incorporation of radioactivity was found in the melanoma. A maximum ¹⁴C concentration ratio of melanoma: serum of 4 was attained at 24 hr. Radioactivity in a more pigmented area of a Syrian hamster melanoma varied from 6.3 to 33.4 times that of serum. The uptake of ¹⁴C appeared to depend to a large extent upon the degree of pigmentation. Pretreatment with pyrogallol, a competitive inhibitor of catechol-o-methyl-transferase, the enzyme most responsible for the degradation of circulating catecholamines, did not enhance uptake in the melanoma but significantly enhanced the uptake in the adrenal gland. Administration of ¹⁴C- and ¹²⁵I-labeled 5,6-diacetoxyindole derivatives failed to result in concentration of radioactivity in melanoma or adrenal, possibly because an earlier precursor of melanin enters the melanosome before these late metabolic steps occur.

¹ This work was supported by grants from the NIH, CA-5134-03 and CA-08429-02, the Michigan Memorial Phoenix Project, #317, the Nuclear Medicine Research Fund, and the American Cancer Society, PRA-18.

Received 12/22/66. Accepted 4/ 4/67.